Wintermeyer, Wolfgang

[["dc.bibliographiccitation.firstpage","1183"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.bibliographiccitation.lastpage","1194"],["dc.bibliographiccitation.volume","343"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Savelsbergh, Andreas"],["dc.contributor.author","Katunin, Vladimir I."],["dc.contributor.author","Rodnina, Marina"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.date.accessioned","2017-09-07T11:43:10Z"],["dc.date.available","2017-09-07T11:43:10Z"],["dc.date.issued","2004"],["dc.description.abstract","Translocation, a coordinated movement of two tRNAs together with mRNA on the ribosome, is catalyzed by elongation factor G (EF-G). The reaction is accompanied by conformational rearrangements of the ribosome that are, as yet, not well characterized. Here, we analyze those rearrangements by restricting the conformational flexibility of the ribosome by antibiotics binding to specific sites of the ribosome. Paromomycin (Par), viomycin (Vio), spectinomycin (Spc), and hygromycin B (HygB) inhibited the tRNA-mRNA movement, while the other partial reactions of translocation, including the unlocking rearrangement of the ribosome that precedes tRNA-mRNA movement, were not affected. The functional cycle of EF-G, i.e. binding of EF-G(.)GTP to the ribosome, GTP hydrolysis, Pi release, and dissociation of EF-G(.)GDP from the ribosome, was not affected either, indicating that EF-G turnover is not coupled directly to tRNA-mRNA movement. The inhibition of translocation. by Par and Vio is attributed to the stabilization of tRNA binding in the A site, whereas Spc and HygB had a direct inhibitory effect on tRNA-mRNA movement. Streptomycin (Str) had essentially no effect on translocation, although it caused a large increase in tRNA affinity to the A site. These results suggest that conformational changes in the vicinity of the decoding region at the binding sites of Spc and HygB are important for tRNA-mRNA movement, whereas Str seems to stabilize a conformation of the ribosome that is prone to rapid translocation, thereby compensating the effect on tRNA affinity. (C) 2004 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.jmb.2004.08.097"],["dc.identifier.gro","3143929"],["dc.identifier.isi","000224838800003"],["dc.identifier.pmid","15491605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1497"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd Elsevier Science Ltd"],["dc.relation.issn","0022-2836"],["dc.title","Conformational changes of the small ribosomal subunit during elongation factor G-dependent tRNA-mRNA translocation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","7442"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Senyushkina, Tamara"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Fischer, Niels"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2015"],["dc.description.abstract","The coupled translocation of transfer RNA and messenger RNA through the ribosome entails large-scale structural rearrangements, including step-wise movements of the tRNAs. Recent structural work has visualized intermediates of translocation induced by elongation factor G (EF-G) with tRNAs trapped in chimeric states with respect to 30S and 50S ribosomal subunits. The functional role of the chimeric states is not known. Here we follow the formation of translocation intermediates by single-molecule fluorescence resonance energy transfer. Using EF-G mutants, a non-hydrolysable GTP analogue, and fusidic acid, we interfere with either translocation or EF-G release from the ribosome and identify several rapidly interconverting chimeric tRNA states on the reaction pathway. EF-G engagement prevents backward transitions early in translocation and increases the fraction of ribosomes that rapidly fluctuate between hybrid, chimeric and posttranslocation states. Thus, the engagement of EF-G alters the energetics of translocation towards a flat energy landscape, thereby promoting forward tRNA movement."],["dc.identifier.doi","10.1038/ncomms8442"],["dc.identifier.gro","3141892"],["dc.identifier.isi","000357176700008"],["dc.identifier.pmid","26072700"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2234"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2041-1723"],["dc.title","Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","559"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular Biology"],["dc.bibliographiccitation.lastpage","568"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Rodnina, Marina"],["dc.contributor.author","Semenkov, Yuri P."],["dc.contributor.author","Savelsbergh, Andreas"],["dc.contributor.author","Katunin, Vladimir I."],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Wilden, Berthold"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.date.accessioned","2017-09-07T11:46:05Z"],["dc.date.available","2017-09-07T11:46:05Z"],["dc.date.issued","2001"],["dc.description.abstract","During the translocation step of the elongation cycle of peptide synthesis two tRNAs together with the mRNA move synchronously and rapidly on the ribosome. Translocation is catalyzed by the elongation factor G (EF-G) and requires GTP hydrolysis. The fundamental biochemical features of the process were worked out in the 1970-80s, to a large part by A.S. Spirin and his colleagues. Recent results from pre-steady-state kinetic analysis and cryoelectron microscopy suggest that translocation is a multistep dynamic process that entails large-scale structural rearrangements of both ribosome and EF-G. Kinetic and thermodynamic data, together with the structural information on the conformational changes in the ribosome and EF-G, provide a detailed mechanistic model of translocation and suggest a mechanism of translocation catalysis by EF-G."],["dc.identifier.doi","10.1023/A:1010523026531"],["dc.identifier.gro","3144276"],["dc.identifier.isi","000170715300012"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1882"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Consultants Bureau"],["dc.relation.issn","0026-8933"],["dc.title","Mechanism of tRNA translocation on the ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1073"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The EMBO journal"],["dc.bibliographiccitation.lastpage","1085"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Holtkamp, Wolf"],["dc.contributor.author","Cunha, Carlos E. da"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Konevega, Andrey L."],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2018-01-26T06:04:53Z"],["dc.date.available","2018-01-26T06:04:53Z"],["dc.date.issued","2014"],["dc.description.abstract","Elongation factor G (EF-G) promotes the movement of two tRNAs and the mRNA through the ribosome in each cycle of peptide elongation. During translocation, the tRNAs transiently occupy intermediate positions on both small (30S) and large (50S) ribosomal subunits. How EF-G and GTP hydrolysis control these movements is still unclear. We used fluorescence labels that specifically monitor movements on either 30S or 50S subunits in combination with EF-G mutants and translocation-specific antibiotics to investigate timing and energetics of translocation. We show that EF-G-GTP facilitates synchronous movements of peptidyl-tRNA on the two subunits into an early post-translocation state, which resembles a chimeric state identified by structural studies. EF-G binding without GTP hydrolysis promotes only partial tRNA movement on the 50S subunit. However, rapid 30S translocation and the concomitant completion of 50S translocation require GTP hydrolysis and a functional domain 4 of EF-G. Our results reveal two distinct modes for utilizing the energy of EF-G binding and GTP hydrolysis and suggest that coupling of GTP hydrolysis to translocation is mediated through rearrangements of the 30S subunit."],["dc.identifier.doi","10.1002/embj.201387465"],["dc.identifier.pmid","24614227"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11834"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1460-2075"],["dc.title","GTP hydrolysis by EF-G synchronizes tRNA movement on small and large ribosomal subunits"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1197"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","RNA Biology"],["dc.bibliographiccitation.lastpage","1203"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Belardinelli, Riccardo"],["dc.contributor.author","Sharma, Heena"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina"],["dc.date.accessioned","2017-09-07T11:54:04Z"],["dc.date.available","2017-09-07T11:54:04Z"],["dc.date.issued","2016"],["dc.description.abstract","In each round of translation elongation, tRNAs and mRNA move within the ribosome by one codon at a time. tRNA–mRNA translocation is promoted by elongation factor G (EF-G) at the cost of GTP hydrolysis. The key questions for understanding translocation are how and when the tRNAs move and how EF-G coordinates motions of the ribosomal subunits with tRNA movement. Here we present 2 recent papers which describe the choreography of movements over the whole trajectory of translocation. We present the view that EF-G accelerates translocation by promoting the steps that lead to GTPase-dependent ribosome unlocking. EF-G facilitates the formation of the rotated state of the ribosome and uncouples the backward motions of the ribosomal subunits, forming an open conformation in which the tRNAs can rapidly move. Ribosome dynamics are important not only in translocation, but also in recoding events, such as frameshifting and bypassing, and mediate sensitivity to antibiotics."],["dc.identifier.doi","10.1080/15476286.2016.1240140"],["dc.identifier.gro","3145096"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2795"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1547-6286"],["dc.subject","EF-G; mRNA; molecular machines; protein synthesis; ribosome; tRNA; translation; translation elongation; translocation"],["dc.title","Translocation as continuous movement through the ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","377"],["dc.bibliographiccitation.issue","5-6"],["dc.bibliographiccitation.journal","Biological Chemistry"],["dc.bibliographiccitation.lastpage","387"],["dc.bibliographiccitation.volume","381"],["dc.contributor.author","Rodnina, Marina"],["dc.contributor.author","Stark, Holger"],["dc.contributor.author","Savelsbergh, Andreas"],["dc.contributor.author","Wieden, Hans-Joachim"],["dc.contributor.author","Mohr, Dagmar"],["dc.contributor.author","Matassova, Natalia B."],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Daviter, T"],["dc.contributor.author","Gualerzi, Claudio O."],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.date.accessioned","2017-09-07T11:47:23Z"],["dc.date.available","2017-09-07T11:47:23Z"],["dc.date.issued","2000"],["dc.description.abstract","The elongation factors (EF) Tu and G and initiation factor 2 (IF2) from bacteria are multidomain GTPases with essential functions in the elongation and initiation phases of translation. They bind to the same site on the ribosome where their low intrinsic GTPase activities are strongly stimulated. The factors differ fundamentally from each other, and from the majority of GTPases, in the mechanisms of GTPase control, the timing of P-i release, and the functional role of GTP hydrolysis. EF-Tu GTP forms a ternary complex with aminoacyl-tRNA, which binds to the ribosome, Only when a matching codon is recognized, the GTPase of EF-Tu is stimulated, rapid GTP hydrolysis and P-i release take place, EF-Tu rearranges to the GDP form, and aminoacyl-tRNA is released into the peptidyltransferase center. In contrast, EF-G hydrolyzes GTP immediately upon binding to the ribosome, stimulated by ribosomal protein L7/12. Subsequent translocation is driven by the slow dissociation of P-i, suggesting a mechano-chemical function of EF-G, Accordingly, different conformations of EF-G on the ribosome are revealed by cryo-electron microscopy. GTP hydrolysis by IF2 is triggered upon formation of the 70S initiation complex, and the dissociation of P-i and/or IF2 follows a rearrangement of the ribosome into the elongation-competent state."],["dc.identifier.doi","10.1515/BC.2000.050"],["dc.identifier.gro","3144395"],["dc.identifier.isi","000088435900004"],["dc.identifier.pmid","10937868"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2015"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Walter De Gruyter & Co"],["dc.relation.issn","1431-6730"],["dc.title","GTPase mechanisms and functions of translation factors on the ribosome"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","733"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biochemical Society Transactions"],["dc.bibliographiccitation.lastpage","737"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Wintermeyer, W."],["dc.contributor.author","Peske, F."],["dc.contributor.author","Beringer, M."],["dc.contributor.author","Gromadski, K.B."],["dc.contributor.author","Savelsbergh, A."],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2022-03-01T11:46:16Z"],["dc.date.available","2022-03-01T11:46:16Z"],["dc.date.issued","2004"],["dc.description.abstract","Protein synthesis in the cell is performed on ribosomes, large ribonucleoprotein particles, which in bacteria consist of three RNA molecules and over 50 proteins. This review summarizes recent progress in understanding the mechanisms of the elongation phase of protein synthesis. Results from rapid kinetic analysis of elongation reactions are discussed in the light of recent structural data."],["dc.description.abstract","Protein synthesis in the cell is performed on ribosomes, large ribonucleoprotein particles, which in bacteria consist of three RNA molecules and over 50 proteins. This review summarizes recent progress in understanding the mechanisms of the elongation phase of protein synthesis. Results from rapid kinetic analysis of elongation reactions are discussed in the light of recent structural data."],["dc.identifier.doi","10.1042/BST0320733"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103608"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1470-8752"],["dc.relation.issn","0300-5127"],["dc.title","Mechanisms of elongation on the ribosome: dynamics of a macromolecular machine"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","566"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","RNA"],["dc.bibliographiccitation.lastpage","573"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Gu, Shan-Qing"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Wieden, Hans-Joachim"],["dc.contributor.author","Rodnina, Marina"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.date.accessioned","2017-09-07T11:45:01Z"],["dc.date.available","2017-09-07T11:45:01Z"],["dc.date.issued","2003"],["dc.description.abstract","The signal recognition particle (SRP) from Escherichia coli, composed of Ffh protein and 4.5S RNA, mediates membrane targeting of translating ribosomes displaying a signal or signal-anchor sequence. SRP binds at the peptide exit of the large ribosomal subunit. Structural details of the interaction are not known. Here, the position of Ffh or SRP on the ribosome was probed by using site-specific UV-induced crosslinking by rho-azidophenacyl bromide (AzP) attached to a number of cysteine residues engineered into surface positions of Ffh. Efficient crosslinking to vacant ribosomes took place from two positions (AzP17 and AzP25) in the N domain of Ffh, both with Ffh and SRP. Both Azp17 and AzP25 were predominantly crosslinked to ribosomal protein L23 that is located at the peptide exit of the 50S subunit. The SRP receptor, FtsY, did not change the crosslink patten, whereas the presence of a nascent signal peptide on the ribosome resulted in a second crosslinked between Ffh(AzP17) and protein L23, indicating that binding to the nascent signal peptide induced a slightly different arrangement of SRP on the ribosome. These results indicate a model of the topographical arrangement of SRP at the peptide exit of the 50S ribosomal subunit."],["dc.identifier.doi","10.1261/rna.2196403"],["dc.identifier.gro","3144109"],["dc.identifier.isi","000184447700006"],["dc.identifier.pmid","12702815"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1697"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1355-8382"],["dc.title","The signal recognition particle binds to protein L23 at the peptide exit of the Escherichia coli ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2102"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","2107"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Cox, Georgina"],["dc.contributor.author","Thompson, Gary S."],["dc.contributor.author","Jenkins, Huw T."],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Savelsbergh, Andreas"],["dc.contributor.author","Rodnina, Marina V."],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Homans, Steve W."],["dc.contributor.author","Edwards, Thomas A."],["dc.contributor.author","O'Neill, Alexander J."],["dc.date.accessioned","2018-01-29T12:41:47Z"],["dc.date.available","2018-01-29T12:41:47Z"],["dc.date.issued","2012"],["dc.description.abstract","Resistance to the antibiotic fusidic acid (FA) in the human pathogen Staphylococcus aureus usually results from expression of FusB-type proteins (FusB or FusC). These proteins bind to elongation factor G (EF-G), the target of FA, and rescue translation from FA-mediated inhibition by an unknown mechanism. Here we show that the FusB family are two-domain metalloproteins, the C-terminal domain of which contains a four-cysteine zinc finger with a unique structural fold. This domain mediates a high-affinity interaction with the C-terminal domains of EF-G. By binding to EF-G on the ribosome, FusB-type proteins promote the dissociation of stalled ribosome⋅EF-G⋅GDP complexes that form in the presence of FA, thereby allowing the ribosomes to resume translation. Ribosome clearance by these proteins represents a highly unusual antibiotic resistance mechanism, which appears to be fine-tuned by the relative abundance of FusB-type protein, ribosomes, and EF-G."],["dc.identifier.doi","10.1073/pnas.1117275109"],["dc.identifier.pmid","22308410"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11881"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.relation.eissn","1091-6490"],["dc.title","Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","342"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","348"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Belardinelli, Riccardo"],["dc.contributor.author","Sharma, Heena"],["dc.contributor.author","Caliskan, Neva"],["dc.contributor.author","Cunha, Carlos E. da"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2017-09-07T11:54:33Z"],["dc.date.available","2017-09-07T11:54:33Z"],["dc.date.issued","2016"],["dc.description.abstract","During translation elongation, ribosome translocation along an mRNA entails rotations of the ribosomal subunits, swiveling motions of the small subunit (SSU) head and stepwise movements of the tRNAs together with the mRNA. Here, we reconstructed the choreography of the collective motions of the Escherichia coli ribosome during translocation promoted by elongation factor EF-G, by recording the fluorescence signatures of nine different reporters placed on both ribosomal subunits, tRNA and mRNA. We captured an early forward swiveling of the SSU head taking place while the SSU body rotates in the opposite, clockwise direction. Backward swiveling of the SSU head starts upon tRNA translocation and continues until the post-translocation state is reached. This work places structures of translocation intermediates along a time axis and unravels principles of the motions of macromolecular machines."],["dc.identifier.doi","10.1038/nsmb.3193"],["dc.identifier.gro","3141703"],["dc.identifier.isi","000373658300012"],["dc.identifier.pmid","26999556"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/136"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.title","Choreography of molecular movements during ribosome progression along mRNA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]