Groupleader: Irmgard Sinning
Irmgard Sinning
Structural Biology
Research
Prestigious medal from the State of Bavaria for Irmi Sinning
Leibniz-Prize 2014 awarded to Irmgard Sinning
Featured in nature Crystallography at 100 issue
Our mission
Our research aims at the understanding of fundamental cellular processes at atomic detail. Our key interests are the molecular mechanisms of protein homeostasis with focus on cotranslational protein folding, maturation and targeting. Defects in these processes can lead to numerous diseases including neurodegenerative disorders and cancer, which are a threat to our aging society. RNA-protein complexes here include ribosomes and the SRP system. Intrigued by RNA turnover and the importance of non-coding RNAs, we recently embarked on the analysis of a novel exosome adaptor complex. Membrane protein biogenesis extends our long-standing interest in protein targeting. All these processes depend on precisely orchestrated interactions of the proteins and macromolecular assemblies involved with nucleic acids, proteins, membrane lipids and other ligands. We address these topics by a broad methodological spectrum firmly routed by our expertise in macromolecular structure determination.
Our approach
Structural information is the basis to understand the function of macromolecular complexes and their dynamic interplay. We employ integrated structural biology with high-resolution structure determination by cryo-EM and X-ray crystallography in combination with biochemical and biophysical tools (e.g. BLI, MST, ITC, DSF, MALS, HDX-MS, XL-MS, SAXS). State of the art expression and purification strategies are the basis for our studies. Our model systems range from bacteria to eukaryotes and include our pet-eukaryote, the thermophilic fungus Chaetomium thermophilum. With HDcryoNET and the crystallization platform we established a powerful scientific infrastructure.
Cotranslational processes
Ribosomes are among the largest cellular machines and translate the information embedded in the mRNA into polypeptide sequences. However, the activity of ribosomes is not merely restricted to protein synthesis and to ensuring a high fidelity of translation. They are also crucial players in the modification, folding, assembly and membrane-insertion of newly-synthesized polypeptides. Ribosomes provide a binding platform for a whole network of machineries and thereby determine also the fate of nascent polypeptides. The interaction of these factors with the nascent chain requires precise spatio-temporal coordination as many of them interact already with short nascent chains and use overlapping sites nearby the ribosomal tunnel exit. They can be divided into three main classes: transport factors that assist in ER membrane targeting and insertion of membrane proteins (the SRP/SR/Sec61 pathway), chaperones that assist in correct protein folding (NAC, RAC/Ssb), and enzymes involved in nascent chain modification (MetAPs, NATs).
Protein targeting: SRP pathway:
Membrane proteins comprise more than 25% of the cellular proteome and their function depends on insertion into the correct target membrane. Cotranslational targeting by the signal recognition particle (SRP) pathway elegantly couples membrane protein synthesis with membrane insertion by the Sec translocon, and avoids exposure of hydrophobic transmembrane segments prone to aggregation. SRP is a universally conserved protein/RNA complex and the SRP pathway is controlled by a unique set of GTP binding proteins (Kempf et al. 2018; Wild et al. 2016; Montoya et al. 1997), which are regulated by the SRP RNA (reviewed in: Wild et al. 2019; Bange & Sinning 2013). Our goal is to deduce the molecular and structural framework of this multistep regulatory pathway that ensures the fidelity of protein transport. Analysing the first mutations in human SRP54 that cause severe congenital neutropenia as well as Shwachman-Diamond-like disease syndrome is a beautiful example of a detailed QSAR-type study. We showed a critical destabilization of the GTPase that eliminates targeting complex formation with the SRP receptor (Juaire et al. 2021). After showing how SRP RNA remodeling by SRP68/72 supports SRP function in elongation arrest and protein translocation (Grotwinkel et al. 2014; Becker et al, 2017), we recently succeeded in the large scale reconstitution of the complete human SRP system (Wild et al. 2019) opening new avenues for detailed studies.
Protein folding: RAC/Ssb:
Chaperones are essential in promoting correct protein folding in all domains of life. In yeast, the ribosome-associated complex (RAC) consists of the Hsp70 member Ssz1 and its Hsp40 partner Zuo1, which together with Ssb form a functional chaperone triad promoting co-translational folding of nascent chains (reviewed in: Zhang et al. 2017). For a long time, understanding RAC/Ssb function was impeded by the lack of structural information. A previous cryo-EM structure showed the position of yeast RAC at the ribosome, however the limited resolution did not allow to position individual protein domains (Zhang et al. 2014). While it was previously shown that the Ssb ATPase is activated only by the J-domain present in Zuo1, mechanistic details remained unresolved. Using proteins from our thermophilic model organism Chaetomium thermophilum, we obtained first insights into Ssb and RAC (Gumiero et al. 2016; Leidig et al 2013) and showed that Ssb interacts with ribosomal RNA and proteins at the tunnel exit by a conserved cluster of positively charged residues at its C-terminus (Gumiero et al. 2016). By structure determination of the RAC core we could show that the non-canonical Hsp70 protein Ssz1 does contain a substrate-binding domain (SBD). However, it lacks the helical lid domain, and the b-sandwich domain (SBDb) is complemented by the Zuo1 N-terminus (Zhang et al. 2020; Weyer et al. 2017). RAC and Ssb cooperate in a relay system at the ribosome to ensure productive nascent chain handover to Ssb (Zhang et al. 2020). One of the current goals is therefore to resolve mechanistic details of nascent chain recognition and handover in the RAC/Ssb relay.
Protein modification: MAPs and NATs:
A vast majority of nascent polypeptides in eukaryotes experience removal of the N-terminal methionine by ribosome-associated methionine-aminopeptidases (MAPs). Several protein factors that share the MAP-fold, but have no enzymatic activity occupy the putative MAP binding site. These include the ribosome-biogenesis factor Arx1 (Kater et al. 2017; Bradatsch et al. 2007) and Ebp1, which plays an important role in cancer regulation (Wild et al. 2020; Kowalinski et al. 2007). While structural information on 80S/MAP interaction is still missing, the eukaryote specific expansion segment 27 (ES27) seems to play an important role in orchestrating these proteins. Current studies using single-particle cryo-EM address this point.
N-terminal acetylation of nascent protein chains is one of the most common co-translational modifications in eukaryotes. Over 80% of all cytosolic proteins in mammals and more than 40% of all proteins in the yeast Saccharomyces cerevisiae are acetylated by Nα-terminal acetyltransferase complexes (NATs). The precise physiological role of this modification is still not established. However, it has been implicated in protein complex assembly, protein targeting, turnover and quality control. Five different NATs (NatA to NatE) modify each a distinct selection of cellular proteins due to different substrate specificities. NATs consist of at least two subunits, i.e. a ribosomal adapter (auxiliary subunit) and the catalytic subunit, which bind close to the ribosomal tunnel exit. However, the activity of NatA, which has the largest set of substrates, is regulated by additional factors: Naa50 and HypK. We showed that HypK in vitro serves by inhibiting NatA activity (Weyer et al. 2017) and that Naa50 has different, organism-specific roles in NatA regulation (Weidenhausen et a. 2021). NatB differs in substrate specificity and in catalytic activity of Naa20 alone (without its ribosome adaptor) (Layer et al. 2021; Huber et al. 2020). A long-term goal is to dissect the interplay between these enzymes and chaperones on nascent chains emerging from a translating ribosome.
Membrane protein insertion: the GET pathway
Targeting and insertion of membrane proteins into the correct membrane presents a challenge for the chaperones and machinery involved. The SRP system relies on the presence of an N-terminal signal sequence that is recognized in context of a translating ribosome. However, a subset of membrane proteins involved in important physiological processes ranging from intracellular trafficking to protein degradation and programmed cell death lack such a signal sequence. Instead they carry their targeting signal at the C-terminus and are therefore termed tail-anchored (TA) proteins. These proteins are targeted to the ER post-translationally by the GET pathway (guided entry of tail-anchored proteins). Such post-translational system requires a whole chaperone cascade to direct the TA proteins safely to the ER membrane for insertion. While the components of the GET pathway have been identified in the last decade, the molecular and structural framework especially of the ER insertion steps was lagging far behind our understanding e.g. of the SRP/Sec system. We set out to fill this gap by determining key structures on the involved machinery starting with the Get3 chaperone (Bozkurt et al. 2009) and its interaction with the Get1/Get2 insertase (Denic et al 2013; Stefer et al. 2011). Our recent cryo-EM structure of the human GET insertase (McDowell et al. 2020) shows a lipid-stabilized heterotetramer with a membrane-embedded hydrophilic groove and an unanticipated, conserved cytoplasmic helix, and reveals a striking structural homology between Get1 homologs and their bacterial counterpart YidC (McDowell et al. 2021). These structural details are the basis for further studies to understand the mechanisms of TA protein insertion and the role of dynamic membrane remodeling by insertase/lipid interactions.
Download BZH Report Sinning 2014-2016
CV
| 1989 |
PhD (Biochemistry), University of Munich, with H. Michel (MPI Martinsried) |
| 1989-1991 |
Postdoc with H. Michel (Biochemistry/Structural Biology), MPI-Biophysics Frankfurt |
| 1991-1993 |
Postdoc with T.A. Jones (Structural Biology), BMC University of Uppsala, Sweden |
| 1994-1999 |
Group Leader (Structural Biology Programme), EMBL Heidelberg |
| since 2000 |
C4/W3 Professor for Biochemistry/Structural Biology at the Heidelberg University Biochemistry Center (BZH) |
| 2006-2009 |
Director of the Heidelberg University Biochemistry Center (BZH) |
| 2010 |
Elected EMBO Member |
| 2010 |
Elected Member of Leopoldina |
| 2016 |
Elected member of Heidelberg Academy of Sciences and Humanities |
| 2019 |
Elected member of Berlin-Brandenburgische Akademie der Wissenschaften (BBAW) |
Lab Members
TA
Lab:Room 526
/ Phone: +49 6221 54-4787
Office:Room 526 a
/ Phone: +49 6221 54-4787
Mail:silke.adrian@bzh.uni-heidelberg.de
PhD student
Lab:Room 524
/ Phone: +49 6221 54-4782
Office:Room 524
/ Phone: +49 6221 54-4782
Mail:michael.heimes@bzh.uni-heidelberg.de
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TA
Lab:Room 524 a
/ Phone: +49 6221 54-4784
Office:Room 524 a
/ Phone: +49 6221 54-4784
Mail:astrid.hendricks@bzh.uni-heidelberg.de
TA
Lab:Room 526
/ Phone: +49 6221 54-4789
Office:Room 526 b
/ Phone: +49 6221 54-4789
Mail:elke.herwig@bzh.uni-heidelberg.de
postdoc
Lab:Room 526
/ Phone: +49 6221 54-4787
Office:Room 506
/ Phone: +49 6221 54-4788
Mail:nikola.kellner@bzh.uni-heidelberg.de
PhD student
Lab:Room 524
/ Phone: +49 6221 54-4782
Office:Room 524
/ Phone: +49 6221 54-4782
Mail:marius.klein@bzh.uni-heidelberg.de
TA
Lab:Room 122
/ Phone: +49 6221 54-4336
Mail:britta.klem@bzh.uni-heidelberg.de
scientific staff
Lab:Room 265
/ Phone: +49 6221 54-4112
Office:Room 267
/ Phone: +49 6221 54-4481
Mail:juergen.kopp@bzh.uni-heidelberg.de
Leiter Kristallisationsplattform Cell Networks
PhD student
Lab:Room 524
/ Phone: +49 6221 54-4786
Office:Room 524
/ Phone: +49 6221 54-4786
Mail:dominik.layer@bzh.uni-heidelberg.de
research assistant
Lab:Room 524
/ Phone: +49 6221 54-4786
Office:Room 524
/ Phone: +49 6221 54-4786
Mail:Marz@stud.uni-heidelberg.de
scientific staff
Office:Room 108
/ Phone: +49 6221 54-4783
Mail:lutz.nuecker@bzh.uni-heidelberg.de
TA
Lab:Room 524a
/ Phone: +49 6221 54-4786
Mail:marina.pelzl@bzh.uni-heidelberg.de
Auch im Raum 246 unter -4524 erreichbar!
PhD student
Lab:Room 526
/ Phone: +49 6221 54-4796
Office:Room 526
/ Phone: +49 6221 54-4796
Mail:merlin.schwan@bzh.uni-heidelberg.de
TA
Lab:Room 266
Office:Room 265
/ Phone: +49 6221 54-4112
Mail:claudia.siegmann@bzh.uni-heidelberg.de
Mitarbeiterin Kristallisationsplattform Cell Networks
postdoc
Lab:Room 524
/ Phone: +49 6221 54-4784
Office:Room 506
/ Phone: +49 6221 54-4788
Mail:komal.soni@bzh.uni-heidelberg.de
others
Lab:Room 526
/ Phone: +49 6221 54-4789
Office:Room 526 b
/ Phone: +49 6221 54-4789
Mail:gunter.stier@bzh.uni-heidelberg.de
PhD student
Lab:Room 526
/ Phone: +49 6221 54-4796
Office:Room 526
/ Phone: +49 6221 54-4796
Mail:andrea.svorinic@bzh.uni-heidelberg.de
secretary
Office:Room 507
/ Phone: +49 6221 54-4780
Mail:anja.weber@bzh.uni-heidelberg.de
PhD student
Lab:Room 524 c
/ Phone: +49 6221 54-4786
Office:Room 524 c
/ Phone: +49 6221 54-4786
Mail:jonas.weidenhausen@bzh.uni-heidelberg.de
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staff scientist
Office:Room 509
/ Phone: +49 6221 54-4785
Mail:klemens.wild@bzh.uni-heidelberg.de
Publications
2021
Dobrev, N., Ahmed, Y.L., Sivadas, A., Fischer*, T. & Sinning*, I. (2021) Red1 orchestrates MTREC submodules and binds the Mtl1 helicase arch domain via its zinc-finger domain, Nat Comms. 12: 3456. PMID: 34103492.
Soni, K., Kempf, G., Manalastas-Cantos, K., Hendricks, A., Flemming, D., Guizetti, J., Simon, B., Frischknecht, F., Svergun, D.I., Wild, K., & Sinning, I. (2021) Structure analysis of the SRP Alu domain from Plasmodium falciparum reveals a non-canonical open conformation, Comms. Biol. 4: 600. PMID: 34017052.
Schürch, C., Schaefer, T., Müller, J.S., Hanns, P., Schärer, J., Sinning, I., Wild, K., Skokowa, J., Welte, K., Carapito, R., Bahram, S., Konantz, M. & Lengerke, C. (2021) SRP54 mutations induce Congenital Neutropenia via dominant-negative effects on XBP1 splicing, Blood, 2020008115. PMID: 33227812.
McDowell, M.A., Heimes, M. & Sinning, I. (2021) Structural and molecular mechanisms for membrane protein biogenesis by the Oxa1 superfamily, Nat. Struct. Mol. Biol. 28: 234-239. PMID: 33664512.
Weidenhausen, J., Kopp, J., Armbruster, L., Wirtz, M., Lapouge, K. & Sinning, I. (2021) Structural and functional characterization of Arabidopsis thaliana N-terminal acetyltransferase Naa50, Structure S0969-2126(20)30471-8. PMID: 33400917.
Layer, D., Kopp, J., Fontanillo, M., Köhn, M., Lapouge, K. & Sinning, I. (2021) Structural basis of Naa20 activity towards a canonical NatB substrate, Comms. Biol. 4: 2. PMID: 33398031
Juaire, K.D., Lapouge, K., Becker, M.M.M., Kotova, I., Michelhans, M., Carapito, R., Wild, K., Bahram, S. & Sinning, I. (2021) Molecular mechanisms of congenital neutropenia linked to mutations in the SRP54 GTPase, Structure, S0969-2126(20)30333-6. PMID: 33053321.
2020
Chiapparino#, A., Grbavac#, A., Jonker, H.R.A., Hackmann, Y., Mortensen, S., Zatorska, E., Schott, A., Stier, G., Saxena, K., Wild, K., Schwalbe, H., Sabine Strahl*, S. & Sinning*, I. (2020) Functional implications of MIR domains in protein O-mannosylation, eLife 9: e61189. PMID: 33357379.
Kurth, M., Lolicato, F., Sandoval-Perez, A., Amaya-Espinosa, H., Teslenko, A., Sinning, I., Beck, R., Brügger B. & Aponte-Santamaria, C.A. (2020) Cholesterol localization around the metabotropic glutamate receptor 2, J. Phys. Chem. B 24: 9061-9078. PMID: 32954729.
McDowell*, M.A., Heimes, M., Fiorentino, F., Mehmood, S., Farkas, Á., Coy-Vergara, J., Wu, D., Schmid, V., Heinze, R., Reddy Bolla, J., Wild, K., Flemming, D., Pfeffer, S., Schwappach, B., Robinson, C.V. & Sinning*, I. (2020) Structural basis of tail-anchored membrane protein biogenesis by the GET insertase complex, Mol Cell 80: 72-86.e7. PMID: 32910895.
Malsam, J., Bärfuss, S., Trimbuch, T., Zarebidaki, F., Sonnen, A.F.-P., Wild, K., Scheutzow, A., Sinning, I., Briggs, J.A.G., Rosenmund, C., and Söllner, T.H. (2020) Complexin suppresses spontaneous exocytosis by capturing the membrane-proximal regions of VAMP2 and SNAP25, Cell Reports, 32: 107926.
Armbruster, L., Linster, E., Boyer, J.B., Brünje, A., Eirich, J., Stephan, I., Bienvenut, W.V., Weidenhausen, J., Meinnel, T., Hell, R., Sinning, I., Finkemeier, I., Giglione,G. & Wirtz, M. (2020) NAA50 is an enzymatically active Nα-acetyltransferase that is crucial for the development and regulation of stress responses, Plant Physiol. 183: 1502-1516.
Linster#, E., Layer#, D., Bienvenut, W.V., Dinh-Van, T., Weyer, F., Lemhuis, W., Brünje, A., Hoffrichter, M., Miklankova, P., Sindlinger, J., Schwarzer, D., Kopp, J., Lapouge, K., Meinnel, T., Giglione, C., Finkemeier, I., Hell, R., Sinning*, I. & Wirtz*, M. (2020) The Arabidopsis Nα-acetyltransferase NAA60 locates to the plasma membrane and is vital for the high salt stress response, New Phytologist, doi: 10.1111/nph.16747. Online ahead of print. PMID: 32548857
Sloan, J., Hakenjos, J.P., Gebert, M., Ermakova, O., Gumiero, A., Stier, G., Wild, K., Sinning*, I. & Lohmann*, J.U. (2020) Structural basis for the complex DNA binding behaviour of the plant stem cell regulator WUSCHEL, Nat. Comms. 11: 2223. PMID: 32376862.
Zhang*, Y., Valentín Gesé*, G., Conz, C., Lapouge, L., Kopp, J., Wölfle, T., Rospert, S. & Sinning, I. (2020) The ribosome-associated complex RAC serves in a relay that directs nascent chains to Ssb, Nat Comms. 11: 1504. PMID: 32198371.
Wild, K., Aleksić, M., Lapouge, K., Juaire, K.D., Flemming, D., Pfeffer, S. & Sinning, I. (2020) MetAP-like Ebp1 occupies the human ribosomal tunnel exit and recruits flexible rRNA expansion segments, Nat Comms. 11: 776. PMID: 32034140.
Huber, M., Bienvenut, W.V., Linster, E., Stephan, I., Armbruster, L., Sticht, C., Layer, D., Lapouge, K., Meinnel, T., Sinning, I., Giglione, C., Hell, R. & Wirtz, M. (2020) N-terminal acetylation by NatB affects growth and abiotic stress responses in Arabidopsis, Plant Physiol. 182: 792-806. PMID: 31744933.
2019
Frindert, J., Kahloon, M.A., Zhang, Y., Ahmed, Y.L., Sinning, I., & Jäschke, A. (2019) Identification of YvcI as novel RNA pyrophospho-hydrolase from B. subtilis, J. Biol. Chem. 94: 19967-19977. PMID: 31740579.
Wild, K., Becker, MMM, Kempf, G. & Sinning, I. (2019) Structure, dynamics, and interactions of large SRP variants (review), Biol. Chem. 401: 63-80. PMID: 31408431.
Ahmed, Y.L., Thoms, M., Mitterer, V., Sinning*, I. & Hurt*, E. (2019) Crystal structures of a Rea1-MIDAS bound to its ribosome assembly factor ligands resembling integrin–ligand-type complexes, Nat. Comms 10: 3050. PMID: 31296859.
Himmelreich N, Dimitrov B, Geiger V, Zielonka M, Hutter AM, Beedgen L, Hüllen A, Breuer M, Peters V, Thiemann KC, Hoffmann GF, Sinning I, Dupré T, Vuillaumier-Barrot S, Barrey C, Denecke J, Kölfen W, Düker G, Ganschow R, Lentze MJ, Moore S, Seta N, Ziegler A, Thiel C. (2019) Novel variants and clinical symptoms in four new ALG3-CDG patients, review of the literature, and identification of AAGRP-ALG3 as a novel ALG3 variant with alanine and glycine-rich N-terminus. Hum Mutat. 40: 938-951. PMID: 31067009.
Wild, K., D. Juaire, K.D., Soni, K., Shanmuganathan, V., Hendriks, A., Segnitz, B., Beckmann, R. & Sinning, I. (2019) Reconstitution of the human SRP system and quantitative and systematic analysis of its ribosome interactions, Nucl. Acids Res. 47: 3184-3196.
2018
Kempf, G., Stjepanovic, G., Hendricks, A., Lapouge, K., & Sinning, I. (2018) The Escherichia coli SRP receptor forms a homodimer at the membrane, Structure 26:1440-1450.e5. PMID: 30146170.
Ahmed, Y.L., Schleich, S., Bohlen, J., Mandel, N., Simon, B., Sinning*, I. & Teleman*, A.A. (2018) DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation. PLoS Biol. 16: e2005160. PMID: 29889857.
2017
Kater, L., Thoms, M., Barrio Garcia, C., Cheng, J., Ismail, S., Ahmed, Y.L., Bange, G., Kressler, D., Berninghausen, O., Sinning, I., Hurt, E. & Beckmann, R. (2017) Visualizing the assembly pathway of nucleolar pre-60S ribosomes, Cell 171: 1599-1610.
Sá-Moura, B., Kornprobst, M., Kharde, S., Ahmed, Y.L., Stier, G., Kunze, R., Sinning*, I. & Hurt*, E. (2017) Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome, PlosOne 12: e0183272.
Zhang, Y., Sinning, I. & Rospert, S. (2017) Two chaperones locked in an embrace: Structure and function of the ribosome-associated complex RAC, Nat. Struct. Mol. Biol. 24: 611-619.
Dodonova, S.O., Aderhold, P., Kopp, J., Ganeva, I., Röhling, S., Hagen, W.J.H., Sinning, I., Wieland, F., & Briggs, J.A.G. (2017) 9Å structure of COPI coat reveals that the Arf1 GTPase occupies two contrasting molecular environments, Elife 6. pii: e26691.
Calviño, F.R., Kornprobst, M., Schermann, G., Birkle, F., Wild, K., Fischer, T., Hurt, E., Ahmed, Y.L. & Sinning, I. (2017) Structural basis for 5’-ETS recognition by Utp4 at the earliest step of ribosome biogenesis, PlosOne 12: e0178752.
Feilen, L.P., Haubrich, K., Strecker, P., Probst, S., Eggert, S., Stier, G., Sinning, I., Konietzko, U., Kins, S., Simon, B. & Wild, K. (2017) Fe65-PTB2 dimerization mimics Fe65-APP interaction, Front. Mol Neurosci. 10: 140.
Weyer, F.A., Gumiero, A., Lapouge, K., Bange, G., Kopp, J. & Sinning, I. (2017) Structural basis of HypK regulating N-terminal acetylation by the NatA complex, Nat Comms 8: 15726.
Rodrigues, M.J., Windeisen, V., Zhang,Y., Guédez,G., Weber, S., Strohmeier, M., Hanes, J.W., Royant, A., Evans, G., Sinning, I., Ealick, S.E., Begley, T.P. & Tews, I. (2017) Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis, Nat. Chem. Biol. 3: 290-294.
Korytowski, A., Abuillan, W., Amadei, F., Makky, A., Gumiero, A., Sinning, I., Gauss, A., Stremmel, W. & Tanaka, M. (2017) Accumulation of phosphatidylcholine on gut intestinal mucosa surface is not dominated by electrostatic interactions, BBA Biomembranes 1859: 959-965.
Weyer, F. A., Gumiero, A., Valentín Gesé, G., Lapouge, K. & Sinning, I. (2017) Structural insights into a unique Hsp70/Hsp40 interaction in the eukaryotic ribosome-associated complex, Nat. Struct. Mol. Biol. 24:144-151.
Becker, M.M.M., Lapouge, K., Segnitz, B., Wild, K. & Sinning, I. (2017) Structures of human SRP72 reveal its function in co-translational protein targeting, Nucl. Acids Res. 45: 470-481.
Baßler, J., Ahmed, Y.L., Kallas, M., Kornprobst, M., Rodriguez-Calvino, F., Gnädig, M., Thoms, M., Stier, G., Ismail, S., Kharde, S., Castillo, N., Griesel, S., Bastuck, S., Bradatsch, B., Thomson, E., Flemming, D., Sinning, I.* & Hurt, E.* (2017) Interaction network of the ribosome assembly machinery from a eukaryotic thermophile, Protein Science 26: 327-342.
2016
Ohle, C., Tesorero, R., Schermann, G., Dobrev, N., Sinning, I. & Fischer, T. (2016) RNA-DNA hybrids and RNase H activity are required for efficient DSB repair, Cell 167: 1001-13.
Gumiero, A., Conz, C., Valentín Gesé, G., Zhang, Y., Weyer, F. A., Lapouge, K., Kappes, J., von Plehwe, U., Schermann, G., Fitzke, E., Wölfle, T., Fischer, T., Rospert, S. & Sinning, I. (2016) Interaction of the cotranslational Hsp70 Ssb with ribosomal proteins and rRNA depends on its lid domain, Nat. Comms. 7: 13563.
Wild, K., Bange, G., Motiejunas, D., Kribelbauer, J., Hendricks, A., Segnitz, B., Wade, R., & Sinning, I. (2016) Structural basis for conserved regulation and adaptation of the signal recognition particle targeting complex, J. Mol. Biol. 428: 2880-97.
Thoms, M., Ahmed. Y.L., Maddi, K., Hurt, E. & Sinning, I. (2016) Concerted removal of the Erb1-Ytm1 complex in ribosome biogenesis relies on an elaborate interface, Nucl. Acids Res. 44: 926-39.
2015
Horn, A., Hennig, J., Ahmed, J.L., Stier, G., Wild, K., Sattler, M. & Sinning, I. (2015) Structural basis for cpSRP43 chromodomain selectivity and dynamics in Alb3 insertase interaction, Nat Comms. 6: 8875.
Jadhav, B., McKenna, M., Johnson, N., High, S., Sinning, I. & Pool, M.R. (2015) Mammalian SRP receptor switches the Sec61 translocase from Sec62 to SRP-dependent translocation, Nat Comms. 6: 10133.
Beckert, B., Kedrov, A., Sohmen, D., Kempf, G., Wild, K., Sinning, I., Stahlberg, H., Wilson, D. & Beckmann, R. (2015) Translational arrest by a prokaryotic signal recognition particle is mediated by RNA interactions, Nat. Struct. Mol. Biol. 22: 767-73.
Jadhav, B., Wild, K., Pool, M.R. & Sinning, I. (2015) Structure and switch cycle of SRβ as ancestral eukaryotic GTPase associated with secretory membranes, Structure 23: 1838-47.
Bassler, J., Paternoga, H., Holdermann, I., Thoms, M., Grannemann, S., Barrio-Garcia, C., Nyarko, A., Lee, W. Stier, G., Clark, S., Schraivogel, D., Kallas, M., Beckmann, R., Tollervey, D., Barbar, E., Sinning*, I. & Hurt*, E. (2015) A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation, J. Cell Biol. 210: 169-70.
Kharde, S., Calviño, F.R., Gumiero, A., Wild, K. & Sinning, I. (2015) The structure of Rpf2-Rrs1 explains its role in ribosome biogenesis, Nucl. Acids Res. 43: 7083-95.
Pausch, P., Singh, U., Ahmed, Y.L., Pillet, B., Altegoer, F., Stier, G., Thoms, M., Hurt, E., Sinning, I., Bange, G. & Kressler, D. (2015) Co-translational capturing of nascent ribosomal proteins by their dedicated chaperones, Nat. Comms 6:7494.
Kempf, G., Wild, K. & Sinning, I. (2015) Strukturelle Evolution des Signalerkennungspartikels, Biospektrum 02: 161-163.
Calviño, F.R., Kharde, S., Ori, A., Hendricks, A., Wild, K., Kressler, D., Bange, G., Hurt, E., Beck, M. & Sinning, I. (2015) Syo1 chaperones 5S-RNP assembly during ribosome biogenesis by RNA mimicry, Nat. Commun. 6: 6510.
Hackmann, Y., Jödicke, L., Panneels, V. & Sinning, I. (2015) Methods Enzymol. 556: 219-39.
Müller, H.M., Steringer, J.S., Wegehingel, S., Bleicken, S., Münster, M., Dimou, E., Unger, S., Weidmann, G., Andreas H., Garcia-Saez, A., Wild, K., Sinning, I. & Nickel, W. (2015) Formation of Disulfide Bridges Drives oligomerization, membrane pore formation and translocation of fibroblast growth factor 2 to cell surfaces, J. Biol. Chem. 290: 8925-37.
2014
Wild, K. & Sinning, I. (2014) RNA gymnastics in mammalian signal recognition particle assembly, RNA Biol. 11: 1330-1334.
Kempf, G., Wild, K. & Sinning, I. (2014) Structure of the tRNA-like bacterial Alu domain Nucl. Acids Res. 42: 12284-94.
Grotwinkel, J.T., Wild, K., Segnitz, B. & Sinning, I. (2014) SRP RNA remodeling by SRP68 explains its role in protein translocation, Science 344: 101-104. DOI:10.1126/science.1249094.
Bassler, J., Paternoga, H., Holdermann, I., Thoms, M., Grannemann, S., Barrio-Garcia, C., Nyarko, A., Stier, G., Clark, S., Schraivogel, D., Kallas, M., Beckmann, R., Tollervey, D., Barbar, E., Sinning*, I. & Hurt*, E. (2014) A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation, J. Cell Biol. 207: 481-498.
Leidig, C., Thoms, M., Holdermann, I., Bradatsch, B., Berninghausen, O., Bange, G., Sinning, I., Hurt, E. & Beckmann, R. (2014) 60S ribosome biogenesis requires rotation of the 5S ribonucleoprotein particle, Nat. Commun. 5: 3491. doi: 10.1038/ncomms4491.
Parisotto, D., Pfau, M., Scheutzow, A., Wild, K., Mayer, M.P., Malsam, J., Sinning, I. & Söllner, T.H. (2014) An extended helical conformation in Munc18-1 domain 3a provides a template for SNAREpin assembly, J. Biol. Chem., 2014 Feb 14. [Epub ahead of print] PMID: 24532794.
De Franceschi, N., Wild, K., Schlacht, A., Dacks, J.B., Sinning, I. & Filippini, F. (2014) Longin and GAF Domains: Structural Evolution and Adaptation to the Subcellular Trafficking Machinery. Traffic 15: 104-21.
2013
Denic, V., Doetsch, V. & Sinning, I. (2013) Endoplasmic reticulum Targeting and Insertion of Tail-anchored membrane proteins by the GET pathway. Cold Spring Harb Perspect Biol. 5(8). doi:pii: a013334.
Bange, G. & Sinning, I. (2013) SIMIBI Twins in protein targeting and localization, Nat. Struct. Mol. Biol. 20:776-80. doi: 10.1038/nsmb.2605.
Bange, G. , Murat, G., Sinning, I., Hurt, E. & Kressler, D. (2013) New twist to nuclear import: When two travel together, Com. & Int. Biol. 6:4, e24792; July/August 2013, Landes Bioscience).
van Noort, V., Bradatsch, B., Arumugam, M., Amlacher, S., Bange, G., Creevey, C., Falk, S., Mende, D.R., Sinning, I., Hurt, E. & Bork, P. (2012) Consistent mutational paths predict eukaryotic thermostability, BMC Evol Biol 13: 7.
Leidig, C., Bange, G., Kopp, J., Amlacher, S., Aravind, A., Wickles, S., Witte, G., Hurt, E., Beckmann, R. & Sinning, I. (2013) Structural characterization of a eukaryotic co-translational chaperone, the ribosome-associated complex (RAC), Nat. Struct. Mol. Biol. 20: 23-8.
2012
Kityk, R., Kopp, J., Sinning, I. & Mayer, M.P. (2012) Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones, Mol Cell, 2012 Nov 1. doi:pii: S1097-2765(12)00823-4. 10.1016/j.molcel.2012.09.023.
Kressler*, D., Bange, G. Ogawa, Y., Bradatsch, B., Pratte, D., Strauß, D., Amlacher, S., Yoneda,Y., Katahira, J., Sinning, I.*, & Hurt, E.* (2012) Synchronizing nuclear import of ribosomal proteins with ribosome assembly, Science 338: 666-71.
Tripp, J., Hahn, A., Koenig, P., Flinner, N., Bublak, D., Ertel, F., Brouwer, E.M., Mirus, O., Sinning, I., Tews, I. & Schleiff, E. (2012) Structure and conservation of the periplasmic targeting factor tic22 protein from plants and cyanobacteria, J. Biol. Chem. 287: 24164-73.
Guédez, G., Hipp, K., Windeisen, V., Derrer, B., Gengenbacher, M., Böttcher, B., Sinning, I., Kappes, B. & Tews, I. (2012) Assembly of the eukaryotic PLP-synthase complex from Plasmodium and activation of the Pdx1 enzyme, Structure 20:172-84.
Holdermann, I., Meyer, H., Round, A., Wild, K., Sattler, M. & Sinning, I. (2012) Chromodomains read the arginine code of post-translational targeting, Nat. Struct. Mol. Biol. 19: 260-3.
2011
Klug W, Dietl A, Simon B, Sinning I, Wild K. Phosphorylation of LRP1 regulates the interaction with Fe65. FEBS Lett. 2011;585: 3229-35.
Sinning, I., Bange, G. & Wild, K. It takes two to Get3. Structure. 2011;19:1353-55.
Bange G, Kümmerer N, Grudnik P, Lindner R, Petzold G, Kressler D, Hurt E, Wild K, Sinning I. Structural basis for the molecular evolution of SRP-GTPase activation by protein. Nat Struct Mol Biol. 2011;8:1376-80.
Pietrosiuk A, Lenherr ED, Falk S, Bönemann G, Kopp J, Zentgraf H, Sinning I, Mogk A. Molecular Basis for the Unique Role of the AAA+ Chaperone ClpV in Type VI Protein Secretion. J Biol Chem. 2011;286(34):30010-21.
Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Löhr F, Bernhard F, Denic V, Dötsch V, Sinning I. Structural basis for tail-anchored membrane protein biogenesis by the Get3-receptor complex. Science. 2011;333(6043):758-62.
Lupo D, Vollmer C, Deckers M, Mick DU, Tews I, Sinning I, Rehling P. Mdm38 is a 14-3-3-Like Receptor and Associates with the Protein Synthesis Machinery at the Inner Mitochondrial Membrane. Traffic. 2011;12 (10):1457-66.
Stjepanovic G, Kapp K, Bange G, Graf C, Parlitz R, Wild K, Mayer MP, Sinning I. Lipids trigger a conformational switch that regulates signal recognition particle (SRP)-mediated protein targeting. J Biol Chem. 2011;286(26):23489-97. Epub 2011 May 3.
Panneels V, Kock I, Krijnse-Locker J, Rezgaoui M, Sinning I. Drosophila photoreceptor cells exploited for the production of eukaryotic membrane proteins: receptors, transporters and channels. PLoS One. 2011;6(4):e18478.
Cain P, Holdermann I, Sinning I, Johnson AE, Robinson C. Binding of chloroplast signal recognition particle to a thylakoid membrane protein substrate in aqueous solution and delineation of the cpSRP43-substrate interaction domain. Biochem J. 2011;437(1):149-55.
Oreb M, Höfle A, Koenig P, Sommer MS, Sinning I, Wang F, Tews I, Schnell DJ, Schleiff E. Substrate binding disrupts dimerization and induces nucleotide exchange of the chloroplast GTPase Toc33. Biochem J. 2011; 436(2):313-9.
2010
Falk S, Sinning I. The C terminus of Alb3 interacts with the chromodomains 2 and 3 of cpSRP43.
J Biol Chem. 2010; 285(53):le25-6;
Erez E, Stjepanovic G, Zelazny AM, Brügger B, Sinning I, Bibi E. Genetic evidence for functional interaction of the Escherichia coli signal recognition particle receptor with acidic lipids in vivo.
J Biol Chem. 2010; 285(52):40508-14.
Derrer B, Windeisen V, Guédez Rodríguez G, Seidler J, Gengenbacher M, Lehmann WD, Rippe K, Sinning I, Tews I, Kappes B. Defining the structural requirements for ribose 5-phosphate-binding and intersubunit cross-talk of the malarial pyridoxal 5-phosphate synthase.
FEBS Lett. 2010; 584(19):4169-74.
Bange G, Kümmerer N, Engel C, Bozkurt G, Wild K, Sinning I. FlhA provides the adaptor for coordinated delivery of late flagella building blocks to the type III secretion system.
Proc Natl Acad Sci U S A. 2010; 107(25):11295-300.
Falk S, Sinning I. cpSRP43 is a novel chaperone specific for light-harvesting chlorophyll a,b-binding proteins.
J Biol Chem. 2010; 285(28):21655-61.
Schott A, Ravaud S, Keller S, Radzimanowski J, Viotti C, Hillmer S, Sinning I, Strahl S. Arabidopsis stromal-derived Factor2 (SDF2) is a crucial target of the unfolded protein response in the endoplasmic reticulum.
J Biol Chem. 2010; 285(23):18113-21.
König P, Mirus O, Haarmann R, Sommer MS, Sinning I, Schleiff E, Tews I. Conserved properties of polypeptide transport-associated (POTRA) domains derived from cyanobacterial Omp85.
J Biol Chem. 2010; 285(23):18016-24.
Bozkurt G, Wild K, Amlacher S, Hurt E, Dobberstein B, Sinning I. The structure of Get4 reveals an alpha-solenoid fold adapted for multiple interactions in tail-anchored protein biogenesis.
FEBS Lett. 2010; 584(8):1509-14.
Schrul B, Kapp K, Sinning I, Dobberstein B. Signal peptide peptidase (SPP) assembles with substrates and misfolded membrane proteins into distinct oligomeric complexes.
Biochem J. 2010; 427(3):523-34.
Wild K, Bange G, Bozkurt G, Segnitz B, Hendricks A, Sinning I. Structural insights into the assembly of the human and archaeal signal recognition particles.
Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 3):295-303.
Panneels V, Sinning I. Membrane protein expression in the eyes of transgenic flies.
Methods Mol Biol. 2010; 601:135-47.
Radzimanowski J, Ravaud S, Schott A, Strahl S, Sinning I. Cloning, recombinant production, crystallization and preliminary X-ray diffraction analysis of SDF2-like protein from Arabidopsis thaliana.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010; 66(Pt 1):12-4.
Falk S, Ravaud S, Koch J, Sinning I. The C terminus of the Alb3 membrane insertase recruits cpSRP43 to the thylakoid membrane.
J Biol Chem. 2010; 285(8):5954-62.
2009
Bozkurt G, Stjepanovic G, Vilardi F, Amlacher S, Wild K, Bange G, Favaloro V, Rippe K, Hurt E, Dobberstein B, Sinning I. Structural insights into tail-anchored protein binding and membrane insertion by Get3.
Proc Natl Acad Sci U S A. 2009; 106(50):21131-6.
Kock I, Bulgakova NA, Knust E, Sinning I, Panneels V. Targeting of Drosophila rhodopsin requires helix 8 but not the distal C-terminus.
PLoS One. 2009; 4(7):e6101.
Grudnik P, Bange G, Sinning I. Protein targeting by the signal recognition particle.
Biol Chem. 2009; 390(8):775-82. Review.
Neuwirth M, Strohmeier M, Windeisen V, Wallner S, Deller S, Rippe K, Sinning I, Macheroux P, Tews I. X-ray crystal structure of Saccharomyces cerevisiae Pdx1 provides insights into the oligomeric nature of PLP synthases.
FEBS Lett. 2009; 583(13):2179-86.
Cross BC, Sinning I, Luirink J, High S. Delivering proteins for export from the cytosol.
Nat Rev Mol Cell Biol. 2009; 10(4):255-64. Review.
Sinning I, Wild K, Bange G. Signal sequences get active.
Nat Chem Biol. 2009; 5(3):146-7.
Wallner S, Neuwirth M, Flicker K, Tews I, Macheroux P. Dissection of contributions from invariant amino acids to complex formation and catalysis in the heteromeric pyridoxal 5-phosphate synthase complex from Bacillus subtilis.
Biochemistry. 2009; 48(9):1928-35.
2008
Bionda T, König P, Oreb M, Tews I, Schleiff E. pH Sensitivity of the GTPase Toc33 as a regulatory circuit for protein translocation into chloroplasts.
Plant Cell Physiol. 2008; 49(12):1917-21.
Oreb M, Tews I, Schleiff E. Policing Tic 'n' Toc, the doorway to chloroplasts.
Trends Cell Biol. 2008; 18(1):19-27. Review.
Radzimanowski J, Simon B, Sattler M, Beyreuther K, Sinning I, Wild K. Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.
EMBO Rep. 2008; 9(11):1134-40.
Beck R, Sun Z, Adolf F, Rutz C, Bassler J, Wild K, Sinning I, Hurt E, Brügger B, Béthune J, Wieland F. Membrane curvature induced by Arf1-GTP is essential for vesicle formation.
Proc Natl Acad Sci U S A. 2008; 105(33):11731-6.
Melchers J, Diechtierow M, Fehér K, Sinning I, Tews I, Krauth-Siegel RL, Muhle-Goll C. Structural basis for a distinct catalytic mechanism in Trypanosoma brucei tryparedoxin peroxidase.
J Biol Chem. 2008; 283(44):30401-11.
Stengel KF, Holdermann I, Cain P, Robinson C, Wild K, Sinning I. Structural basis for specific substrate recognition by the chloroplast signal recognition particle protein cpSRP43.
Science. 2008; 321(5886):253-6.
Radzimanowski J, Ravaud S, Schlesinger S, Koch J, Beyreuther K, Sinning I, Wild K. Crystal structure of the human Fe65-PTB1 domain.
J Biol Chem. 2008; 283(34):23113-20.
König P, Oreb M, Rippe K, Muhle-Goll C, Sinning I, Schleiff E, Tews I. On the significance of Toc-GTPase homodimers.
J Biol Chem. 2008; 283(34):23104-12.
Radzimanowski J, Ravaud S, Beyreuther K, Sinning I, Wild K. Mercury-induced crystallization and SAD phasing of the human Fe65-PTB1 domain.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008; 64(Pt 5):382-5.
Radzimanowski J, Beyreuther K, Sinning I, Wild K. Overproduction, purification, crystallization and preliminary X-ray analysis of human Fe65-PTB2 in complex with the amyloid precursor protein intracellular domain.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008; 64(Pt 5):409-12.
Temmerman K, Ebert AD, Müller HM, Sinning I, Tews I, Nickel W. A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2.
Traffic. 2008; 9(7):1204-17.
Ravaud S, Stjepanovic G, Wild K, Sinning I. The crystal structure of the periplasmic domain of the Escherichia coli membrane protein insertase YidC contains a substrate binding cleft.
J Biol Chem. 2008; 283(14):9350-8.
König P, Oreb M, Höfle A, Kaltofen S, Rippe K, Sinning I, Schleiff E, Tews I. The GTPase cycle of the chloroplast import receptors Toc33/Toc34: implications from monomeric and dimeric structures.
Structure. 2008; 16(4):585-96.
Ravaud S, Wild K, Sinning I. Purification, crystallization and preliminary structural characterization of the periplasmic domain P1 of the Escherichia coli membrane-protein insertase YidC.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008; 64(Pt 2):144-8.
2007
Stengel KF, Holdermann I, Wild K, Sinning I. The structure of the chloroplast signal recognition particle (SRP) receptor reveals mechanistic details of SRP GTPase activation and a conserved membrane targeting site.
FEBS Letters 2007, 581:5671-6.
Bange G, Wild K, Sinning I. Protein translocation: Checkpoint role for SRP GTPase activation.
Curr. Biol. 2007, 17:R980-R982.
Parlitz R, Eitan A, Stjepanovic G, Bahari L, Bange G, Bibi E, Sinning I. E. coli SRP-receptor FtsY contains an essential and autonomous membrane-binding amphipathic helix.
J. Biol. Chem. 2007, 282:32176-184.
Bahari L, Parlitz R, Eitan A, Stjepanovic G, Bochkareva ES, Sinning I, Bibi E. Membrane targeting of ribosomes and their release require distinct and separable functions of FtsY.
J. Biol. Chem. 2007, 282:32168-175.
Kowalinski E, Bange G, Bradatsch B, Hurt E, Wild K, Sinning I. The crystal structure of Ebp1 reveals a methionine aminopeptidase fold as binding platform for multiple interactions.
FEBS Letters 2007, 581: 4450-4454.
Bradatsch B, Katahira J, Kowalinski E, Bange G, Yao W, Sekimoto T, Baumgärtel V, Boese G, Bassler J, Wild K, Peters R, Yoneda Y, Sinning I, Hurt E. Arx1 functions as an unorthodox nuclear export receptor for the 60S pre-ribosomal subunit,
Molecular Cell 2007, 27:767-79.
Kowalinski E, Bange G, Wild K, Sinning I. Expression, purification, crystallization and preliminary crystallographic analysis of the proliferation associated protein Ebp1.
Acta Cryst F 2007, 63: 768-770.
Bange G, Petzold G, Wild K, Parlitz RO, Sinning I. The crystal structure of the third SRP GTPase FlhF reveals a homodimer with bound GTP.
Proc. Natl. Acad.Sci. USA 2007, 104: 13621-13625.
Bange G, Petzold G, Wild K, Sinning I. Expression, purification and preliminary crystallographic characterization of FlhF from Bacillus subtilis,
Acta Cryst F. 2007, 63: 449-451.
Findeisen F, Linder JU, Schultz A, Schultz JE, Brügger B, Wieland F, Sinning I, Tews I. The structure of the regulatory domain of the adenylyl cyclase Rv1264 from Mycobacterium tuberculosis with bound oleic acid.
J. Mol. Biol. 2007, 369:1282-95.
Tzvetkova-Chevolleau T, Hutin C, Noël LD, Goforth R, Carde JP, Caffarri S, Sinning I, Groves M, Teulon JM, Hoffman NE, Henry R, Havaux M, Nussaume L. Canonical Signal Recognition Particle Components Can Be Bypassed for Posttranslational Protein Targeting in Chloroplasts.
Plant Cell 2007,19:1635-48.
Peplowska K, Markgraf DF, Ostrowicz CW, Bange G, Ungermann C. The CORVET tethering complex interacts with the yeast Rab5 homolog Vps21 and is involved in endo-lysosomal biogenesis.
Dev Cell. 2007, 12:739-50.
Flicker K, Neuwirth M, Strohmeier M, Kappes B, Tews I, Macheroux P. Structural and Thermodynamic Insights into the Assembly of the Heteromeric Pyridoxal Phosphate Synthase from Plasmodium falciparum.
J Mol Biol. 2007, 374:732-48.
Fitzpatrick TB, Amrhein N, Kappes B, Macheroux P, Tews I, Raschle T. Two independent routes of de novo vitamin B6 biosynthesis: not that different after all. Biochem J. 2007, 407:1-13.
Tambasco-Studart M, Tews I, Amrhein N, Fitzpatrick TB. Functional analysis of PDX2 from Arabidopsis, a glutaminase involved in vitamin B6 biosynthesis.
Plant Physiol. 2007, 144:915-25.
Neuwirth M, Flicker K, Strohmeier M, Tews I, Macheroux P. Thermodynamic characterization of the protein-protein interaction in the heteromeric Bacillus subtilis pyridoxalphosphate synthase.
Biochemistry 2007, 46:5131-9.
2006
Motaal A, Tews I, Schultz JE, Linder JU. Fatty acid regulation of adenylyl cyclase Rv2212 from Mycobacterium tuberculosis H37Rv.
FEBS J. 2006, 273(18):4219-28.
Qbadou S, Becker T, Mirus O, Tews I, Soll J, Schleiff E. The molecular chaperone Hsp90 delivers precursor proteins to the chloroplast import receptor Toc64.
EMBO J. 2006, 25(9):1836-47.
Gengenbacher M, Fitzpatrick TB, Raschle T, Flicker K, Sinning I, Müller S, Macheroux P, Tews I, Kappes B. Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: Biochemical and structural insights.
J Biol Chem. 2006, 281(6):3633-41.
Strohmeier M, Raschle T, Mazurkiewicz J, Rippe K, Sinning I, Fitzpatrick TB, Tews I. Structure of a bacterial pyridoxal 5'-phosphate synthase complex.
Proc Natl Acad Sci U S A. 2006, 103(51):19284-9.
Halic M, Blau M, Becker T, Mielke T, Pool MR, Wild K, Sinning I, Beckmann R. Following the signal sequence from ribosomal tunnel exit to signal recognition particle.
Nature. 2006, 444(7118):507-11.
Halic M, Gartmann M, Schlenker O, Mielke T, Pool MR, Sinning I, Beckmann R. Signal recognition particle receptor exposes the ribosomal translocon binding site.
Science. 2006, 312(5774):745-7.
Schlenker O, Hendricks A, Sinning I, Wild K. The structure of the mammalian signal recognition particle (SRP) receptor as prototype for the interaction of small GTPases with Longin domains.
J Biol Chem. 2006, 281(13):8898-906.
2005
Tews, I., Findeisen, F., Sinning, I., Schultz A., Schultz, J.E. & Linder, J.U. (2005) The structure of a pH sensing mycobacterial adenylyl cyclase holoenzyme, Science 308: 1020-1023.
2004
Luirink, J. & Sinning, I. (2004) SRP-mediated protein targeting: structure and function revisited, BBA Mol. Cell Res. 1694: 17-35.
Wild, K., Halic, M., Sinning, I. & Beckmann, R. (2004) Co-translational protein targeting: SRP meets the ribosome, Nat. Struct. Mol. Biol. 11: 1049-53.
Abell. B., Pool., M., Schlenker, O., Sinning, I. & High, S. (2004) Signal recognition particle mediates posttranslational targeting in eukaryotes, EMBO J. 23:2755-64.
Wild, K., Rosendal, K. & Sinning, I. (2004) A structural step into the SRP cycle, Mol. Microbiol. 53: 357-63.
Serrano, R.L., Kuhn, A., Hendricks, A., Helms, J.B., Sinning, I. & Groves, M.R. (2004) Structural analysis of the human Golgi-associated plant pathogenesis related protein GAPR-1 implicates dimerization as a regulatory mechanism, J. Mol. Biol. 339: 173-83.
Groves, M.R., Kuhn, A., Hendricks, A., Radke, S., Serrano, R.L., Helms, J.B & Sinning, I. (2004) Crystallization of a Golgi-associated PR-1 related protein (GAPR-1) that localizes to lipid-enriched microdomains, Acta Cryst. D60: 730–732.
Dobberstein, B. & Sinning. I. (2004) Structural biology. Surprising news from the PCC. Science 303: 320-2.
Rosendal, K.R., Sinning, I. & Wild, K. (2004) Crystallization and preliminary X-ray diffraction studies of the crenarchaeal SRP core, Acta Cryst. D60: 140-143.
2003
Vasiljev, A., Ahting, U., Nargang, F.E., Go, N.E., Habib, S.J., Kozany, C., Panneels, V., Sinning, I., Prokisch, H., Neupert, W., Nussberger, S. & Rapaport, D. (2003) Reconstituted TOM core complex and Tim9/Tim10 complex of mitochondria are sufficient for translocation of the ADP/ATP carrier across membranes, Mol. Biol. Cell 15: 1445-58.
Rosendal, K.R., Wild, K., Montoya, G. & Sinning, I. (2003) Crystal structure of the complete core of archaeal signal recognition particle and implications for inter-domain communication, Proc. Natl. Acad. Sci. USA 100: 14701-14706.
Eroglu, C., Bruegger, B., Wieland, F. & Sinning, I. (2003) Glutamate binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts. Proc. Natl. Acad. Sci. USA 100: 10219-10224.
Panneels, V., Schüssler, U., Costagliola, S. & Sinning, I. (2003) Choline head groups stabilize the matrix loop regions of the ATP/ADP carrier ScAAC2. Biochem. Biophys. Res. Com. 300: 65-74.
Sprangers, R., Selenko, P., Sattler, M., Sinning, I. & Groves, M.R. (2003) Definition of Domain Boundaries and Crystallization of the SMN Tudor Domain. Acta Cryst. D59: 366-368.
Sprangers, R., Groves, M.R., Sinning, I. & Sattler, M. (2003) High-resolution X-Ray and NMR structures of the SMN Tudor Domain: conformational variation in the binding site for symmetrically dimethylated arginines, J. Mol.Biol. 327: 507-520.
Panneels, V., Eroglu, C., Cronet, P. & Sinning, I. (2003) Pharmacological characterization and immunoaffinity purification of metabotropic glutamate receptor from Drosophila melanogaster overexpressed in SF9 cells, Prot. Exp. Pur. 30: 275-282.
2002
Groves, M., & Sinning, I. (2002) Chapter 6: Protein/Protein Interactions, in “Peptide arrays on membrane supports: Synthesis and applications” (J. Koch and M. Mahler, eds.) Springer Verlag Heidelberg, Germany, pp.83-96.
Wild, K., Weichenrieder, O., Strub, K., Sinning, I. & Cusack, S. (2002) Towards the structure of the mammalian signal recognition particle. Curr. Opin. Struct. Biol.12: 72–81.
Eroglu, C., Cronet, P., Panneels, V., Beaufils, P. & Sinning, I. (2002) Functional reconstitution of purified mGluR overexpressed in the eye of transgenic Drosophila melanogaster, EMBO Rep. 3: 491-496.
Pool, M.R., Stumm, J., Fulga, T.A., Sinning, I. & Dobberstein, B. (2002) Distinct modes of Signal Recognition Particle interaction with the Ribosome, Science 297: 1345-8
2001
Fulga, T., Sinning, I., Dobberstein, B. & Pool, M.R. (2001) SRbeta coordinates signal sequence release from SRP with ribosome binding to the translocon. EMBO J. 20: 2338-47.
Groves M., Mant A., Kuhn A., Koch J, Dubel S., Robinson C. & Sinning I. (2001) Functional characterization of recombinant chloroplast signal recognition particle. J. Biol. Chem. 276: 27778-86.
Wild, K., Sinning, I. & Cusack , S. (2001) Crystal structure of an early protein-RNA assembly complex of human signal recognition particle. Science 294: 598-601.
2000
de Leeuw, E., te Kaat, K., Moser, C., Menestrina, G., Demel, R., de Kruijff, B., Luirink, J. & Sinning, I. (2000) Anionic phospholipids are involved in membrane association of the Signal Recognition Particle receptor FtsY and stimulate its GTPase activity, EMBO J. 19: 531-541.
Brugna, M., Rodgers, S., Schricker, A., Montoya, G., Kazmeier, M., Nitschke, W. & Sinning, I. (2000) A spectroscopic method for observing the domain movement of the Rieske iron sulphur protein, Proc. Natl. Acad. Sci. USA 97: 2069-2074.
Montoya, G., te Kaat, K., Moll, R., Schäfer, G. & Sinning, I. (2000) The crystal structure of the conserved GTPase of SRP54 from the archaeon Acidianus ambivalens and its comparison with related structures suggests a model for the SRP/SR receptor complex, Struct. Fold. Des. 8: 515-525.
Rodgers, S., Moser, C., Martinez-Julvez, M. & Sinning, I. (2000) Deletion of the 6-kDa subunit affects the activity and yield of the bc1 complex from Rhodovulum sulfidophilum. Eur. J. Biochem. 267: 3753-61.
before 2000
Montoya, G., te Kaat, K., Rodgers, S., Nitschke, W. & Sinning, I. (1999) The cytochrome bc1 complex from Rhodovulum sulfidophilum is a dimer with six quinones per monomer and an additional 6-kDa component, Eur. J. Biochem. 259: 709-718.
Montoya, G., te Kaat, K., Moll, R., Schäfer, G. & Sinning, I. (1999) Crystallization and preliminary X-ray diffraction studies on the conserved GTPase domain of the signal recognition particle from Acidianus ambivalens, Acta Cryst. D55: 1949-1951.
Montoya, G., Svensson, C., Savage, H., Schwenn, J.D. & Sinning, I. (1998) Crystallization and preliminary X-ray diffraction study of phospho-adenylylsulphate (PAPS) reductase from E.coli, Acta Cryst. D54: 281-283.
Montoya, G., Svensson, C., Luirink, J. & Sinning, I. (1997) Expression, crystallization and preliminary X-ray diffraction study of FtsY, the docking protein of the signal recognition particle, Proteins 28: 285-288.
Montoya, G., Svensson, C., Luirink, J. & Sinning, I. (1997) Crystal structure of the NG-domain of the signal-recognition particle receptor FtsY, Nature 385: 365-368.
Savage, H., Montoya, G., Svensson, C., Schwenn, J.D. & Sinning, I. (1997) Crystal structure of phospho-adenylyl-sulfate (PAPS) reductase: a new family of adenine nucleotide hydrolases, Structure 5: 895-906.
Moser, C., Mol, O., Goody, R. & Sinning, I. (1997) The SRP receptor of E. coli has a nucleotide exchange factor built in to the GTPase domain, Proc. Natl. Acad. Sci. USA 94: 11339-11344.
Kleywegt, G.J., Zou, J.-Y., Divne, C., Davies, G.J., Sinning, I., Stahlberg, J., Reinikainen, T., Srisodsuk, M., Teeri, T.T. & Jones, T.A. (1997) The crystal structure of the catalytic core domain of endoglucanaseI from Trichoderma resei at 3.6Å resolution, and a comparison with related enzymes. J. Mol. Biol. 272: 383-397.
de Leeuw, E., Poland, D., Mol, O., Sinning, I., ten Hagen-Jongman, C., Oudega, B., Luirink, J. (1997) Membrane association of FtsY, the E. coli SRP receptor. FEBS Lett. 416: 225-229.
Savage, H., Cyrklaff M., Montoya, G., Kühlbrandt, W. & Sinning, I. (1996) Two-dimensional structure of light-harvesting complex II (LHII) from the purple bacterium Rhodovulum sulfidophilum and comparison with LHII from Rhodopseudomonas acidophila, Structure 4: 243-252.
Deisenhofer, J., Epp, O., Sinning, I. & Michel, H., Crystallographic refinement at 2.3 A resolution and refined model of the photosynthetic reaction centre from Rhodopseudomonas viridis (1995) J. Mol. Biol. 246: 429-457.
Björnestedt, R., Stenberg, G., Widersten, M., Board, P., Sinning, I., Jones, T.A. & Mannervik, B. Functional significance of arginine 15 in the active site of human class Alpha glutathione transferase A1-1 (1995) J. Mol. Biol. 247: 765-773.
Cameron, A. D., Sinning, I., l’Hermite, G., Olin, B., Board, P.G., Mannervik, B. & Jones T.A., Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in comple with ethycrynic acid and its glutathione conjugate (1995) Structure 3: 717-727.
Montoya, G., Cyrklaff, M. & Sinning, I. (1995) Two-dimensional crystallization and preliminary structure analysis of light harvesting II (B800-850) complex from the purple bacterium Rhodovulum sulfidophilum. J. Mol. Biol. 250: 1-10.
Savage, H., Cyrklaff, M., Montoya, G., Kuhlbrandt, W. & Sinning, I. (1995) Two-dimensional crystallisation and structure determination of LHII from Rhv. sulfidophilum at 7 Å resolution. in : Photosynthesis : from Light to Biosphere (Mathis, P., ed.) Kluwer Academic Publishers, Dordrecht, Netherlands, pp 239-242.
Leibl, W., Sinning, I., Ewald, G., Michel, H. & Breton, J. (1993) Biochem. 32: 1958-64.
Sinning, I., Kleywegt, G.J., Cowan, S.W., Reinemer, P., Dirr, H.W., Huber, R., Gilliland, G.L., Armstrong, R.N., Ji, X., Board, P., Olin, B., Mannervik, B. & Jones, T.A. (1993) J. Mol. Biol. 232: 192-212.
Sinning, I., Kleywegt, G.J., Mannervik, B., Board, P. & Jones, T.A. (1993) in (Tew, K.D. et al., eds) Structure and function of Glutathione transferases, CRC Press, pp. 75-86.
Mannervik, B., Berhane, K., Björnestedt, R., Board, P., Jones, T.A., Kolm, R.H., Olin, B., Sinning, I., Sroga, G.E., Stenberg, G., Tardioli, S. & Widersten, M. (1993) in (Tew, K.D. et al., eds) Structure and function of Glutathione transferases, CRC Press, pp. 29-38.
Divne C., Sinning, I., Stalberg, J., Pettersson, G., Bailey, M., Siika-aho, M., Margolles-Clark, E., Teeri, T. & Jones, T.A., Crystallization and preliminary X-ray studies on the core proteins of cellobiohydrolase I and endogluconase I from Trichoderma resei (1993) J. Mol. Biol. 234: 905-907.
Mathis, P., Sinning, I. & Michel, H. (1992) Biochem. Biophys. Acta 1098: 151-158.
Sinning, I. (1992) TIBS 17: 150-54.
Baciou, L., Sinning, I. & Sebban, P. (1991) Biochem. 30: 9110- 9116.
Sinning, I., Michel, H., Mathis, P. & Rutherford, A.W. (1990) FEBS Lett. 256: 192-194.
Sinning, I., Koepke, J., Schiller, B., Mathis, P., Rutherford, A.W. & Michel, H. (1990) in (M. Baltscheffsky, ed.) Current Research in Photosynthesis, Vol.I, Kluwer Acad. Publishers, Netherlands, pp. 173-176.
Sinning, I., Koepke, J., Schiller, B. & Michel , H. (1990) Z. Naturforsch. 45c: 455-458.
Michel, H., Sinning, I., Koepke, J., Ewald, G. & Fritzsch, G. (1990) Biochem. Biophys. Acta 1018: 115-118.
Sinning, I., Koepke, J. & Michel, H. (1990) in ( M. Michel-Beyerle, ed.) Springer Series in Biophysics: Reaction Center of Photosynthetic Bacteria Vol.6, Springer Verlag, pp. 199-208.
Sinning, I. (1989) Der Elektronenakzeptorkomplex im photosynthetischen Reaktionszentrum des Purpurbakteriums Rps. viridis , in Wissenschaftl. Forschungsbeiträge Biologie, Biochemie, Chemie, Bd. 32, Verlag Intemann, Prien a. Chiemsee, ISBN 3-926323-36-1.
Sinning, I., Michel, H., Mathis, P. & Rutherford, A.W. (1989) Biochem. 28: 5544-5553.
Parak, F., Birk, A., Frolov, E., Goldanskii, V., Sinning, I. & Michel, H. (1989) in (J. Jortner & B. Pullman, eds.) Perspectives in Photosynthesis, Kluwer Academic Publ., Netherlands, pp. 413- 421.
Sinning, I. (1989) Der Elektronenakzeptorkomplex im photosynthetischen Reaktionszentrum des Purpurbakteriums Rps. viridis , in Wissenschaftl. Forschungsbeiträge Biologie, Biochemie, Chemie, Bd. 32, Verlag Intemann, Prien a. Chiemsee, ISBN 3-926323-36-1.
Sinning, I., Michel, H., Mathis, P. & Rutherford, A.W. (1989) Biochem. 28: 5544-5553.
Parak, F., Birk, A., Frolov, E., Goldanskii, V., Sinning, I. & Michel, H. (1989) in (J. Jortner & B. Pullman, eds.) Perspectives in Photosynthesis, Kluwer Academic Publ., Netherlands, pp. 413- 421.
Sinning, I. & Michel, H. (1987) J. Biggins (ed.) Progress in Photosynthesis Res. Vol.III, Martinus Nijhoff Publ., Dordrecht,
Sinning, I. & Michel, H. (1987) Z. Naturforsch. 42c: 751-754.
Collaborations
- Seiamak Bahram, Univ. Strasbourg, France
- Michael Boutros, DKFZ Heidelberg
- Britta Brügger, BZH
- Raphael Carapito, Univ. Strasbourg, France
- Iris Finkemeier, Univ. Münster
- Tamas Fischer, Univ. Canberra, Australia
- Mark Helm, Univ. Mainz
- Andres Jäschke, IPMB Univ. Heidelberg
- Michael Knop, ZMBH Univ. Heidelberg
- Christof Niehrs, DKFZ Heidelberg
- Carol Robinson, Univ. Oxford, UK
- Sabine Rospert, Univ. Freiburg
- Harald Schwalbe, Univ. Frankfurt
- Blanche Schwappach, Univ. Göttingen
- Sabine Strahl, COS Univ. Heidelberg
- Henning Urlaub, MPI BPC and Univ. Göttingen
- Markus Wirtz, COS Univ. Heidelberg
Funding
Current:
- Leibniz Programme of the DFG
- SFB 1036
- SFB 1324
- TRR 83
- TRR 319
- FOR 2509
Open Positions
Please use the Application Form (PDF) provided and fill and save it with Acrobat Reader.
PhD student position in Protein Biochemistry/Structural Biology: Mechanisms of Wnt protein secretion
Postdoc position in Protein Biochemistry/Structural Biology: Structural Basis of O-mannosylation
Postdoc position in Protein Biochemistry/Structural Biology: Membrane remodeling by the tail-anchored protein insertase
Contact
der Universität Heidelberg (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Sekretariat: Anja Weber
