Mittelstät, Jörg

[["dc.bibliographiccitation.firstpage","341"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","351"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Buhr, Florian"],["dc.contributor.author","Jha, Sujata"],["dc.contributor.author","Thommen, Michael"],["dc.contributor.author","Mittelstaet, Joerg"],["dc.contributor.author","Kutz, Felicitas"],["dc.contributor.author","Schwalbe, Harald"],["dc.contributor.author","Rodnina, Marina V."],["dc.contributor.author","Komar, Anton A."],["dc.date.accessioned","2017-09-07T11:54:38Z"],["dc.date.available","2017-09-07T11:54:38Z"],["dc.date.issued","2016"],["dc.description.abstract","In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. Here we show that synonymous codon variants in the gene encoding gamma-B crystallin, a mammalian eye-lens protein, modulate the rates of translation and cotranslational folding of protein domains monitored in real time by Forster resonance energy transfer and fluorescence-intensity changes. Gamma-B crystallins produced from mRNAs with changed codon bias have the same amino acid sequence but attain different conformations, as indicated by altered in vivo stability and in vitro protease resistance. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins. Thus, synonymous codons provide a secondary code for protein folding in the cell."],["dc.identifier.doi","10.1016/j.molcel.2016.01.008"],["dc.identifier.gro","3141730"],["dc.identifier.isi","000372325800004"],["dc.identifier.pmid","26849192"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/435"],["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","1097-4164"],["dc.relation.issn","1097-2765"],["dc.title","Synonymous Codons Direct Cotranslational Folding toward Different Protein Conformations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1104"],["dc.bibliographiccitation.issue","6264"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","1107"],["dc.bibliographiccitation.volume","350"],["dc.contributor.author","Holtkamp, Wolf"],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Jäger, Marcus"],["dc.contributor.author","Mittelstaet, Joerg"],["dc.contributor.author","Komar, Anton A."],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2017-09-07T11:54:52Z"],["dc.date.available","2017-09-07T11:54:52Z"],["dc.date.issued","2015"],["dc.description.abstract","Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding of a small five-helix protein domain-the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK-in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains."],["dc.identifier.doi","10.1126/science.aad0344"],["dc.identifier.gro","3141785"],["dc.identifier.isi","000366422600047"],["dc.identifier.pmid","26612953"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1046"],["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","1095-9203"],["dc.relation.issn","0036-8075"],["dc.title","Cotranslational protein folding on the ribosome monitored in real time"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8158"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","8164"],["dc.bibliographiccitation.volume","286"],["dc.contributor.author","Mittelstaet, Joerg"],["dc.contributor.author","Konevega, Andrey L."],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2017-09-07T11:44:20Z"],["dc.date.available","2017-09-07T11:44:20Z"],["dc.date.issued","2011"],["dc.description.abstract","The accurate decoding of the genetic information by the ribosome relies on the communication between the decoding center of the ribosome, where the tRNA anticodon interacts with the codon, and the GTPase center of EF-Tu, where GTP hydrolysis takes place. In the A/T state of decoding, the tRNA undergoes a large conformational change that results in a more open, distorted tRNA structure. Here we use a real-time transient fluorescence quenching approach to monitor the timing and the extent of the tRNA distortion upon reading cognate or near-cognate codons. The tRNA is distorted upon codon recognition and remains in that conformation until the tRNA is released from EF-Tu, although the extent of distortion gradually changes upon transition from the pre- to the post-hydrolysis steps of decoding. The timing and extent of the rearrangement is similar on cognate and near-cognate codons, suggesting that the tRNA distortion alone does not provide a specific switch for the preferential activation of GTP hydrolysis on the cognate codon. Thus, although the tRNA plays an active role in signal transmission between the decoding and GTPase centers, other regulators of signaling must be involved."],["dc.identifier.doi","10.1074/jbc.M110.210021"],["dc.identifier.gro","3142762"],["dc.identifier.isi","000288013300046"],["dc.identifier.pmid","21212264"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/201"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0021-9258"],["dc.title","Distortion of tRNA upon Near-cognate Codon Recognition 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","2979"],["dc.bibliographiccitation.journal","Philosophical Transactions of the Royal Society B: Biological Sciences"],["dc.bibliographiccitation.lastpage","2986"],["dc.contributor.author","Wohlgemuth, Ingo"],["dc.contributor.author","Pohl, Corinna"],["dc.contributor.author","Mittelstaet, Joerg"],["dc.contributor.author","Konevega, Andrey L."],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2018-01-29T13:36:26Z"],["dc.date.available","2018-01-29T13:36:26Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1098/rstb.2011.0138"],["dc.identifier.eissn","1471-2970"],["dc.identifier.pmid","21930591"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11885"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Evolutionary optimization of speed and accuracy of decoding on the ribosome"],["dc.type","review"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","12289"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","12294"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Rezgui, Vanessa Anissa Nathalie"],["dc.contributor.author","Tyagi, Kshitiz"],["dc.contributor.author","Ranjan, Namit"],["dc.contributor.author","Konevega, Andrey L."],["dc.contributor.author","Mittelstaet, Joerg"],["dc.contributor.author","Rodnina, Marina V."],["dc.contributor.author","Peter, Matthias"],["dc.contributor.author","Pedrioli, Patrick G. A."],["dc.date.accessioned","2018-01-26T08:29:14Z"],["dc.date.available","2018-01-26T08:29:14Z"],["dc.date.issued","2013"],["dc.description.abstract","tRNA modifications are crucial to ensure translation efficiency and fidelity. In eukaryotes, the URM1 and ELP pathways increase cellular resistance to various stress conditions, such as nutrient starvation and oxidative agents, by promoting thiolation and methoxycarbonylmethylation, respectively, of the wobble uridine of cytoplasmic (tK(UUU)), (tQ(UUG)), and (tE(UUC)). Although in vitro experiments have implicated these tRNA modifications in modulating wobbling capacity and translation efficiency, their exact in vivo biological roles remain largely unexplored. Using a combination of quantitative proteomics and codon-specific translation reporters, we find that translation of a specific gene subset enriched for AAA, CAA, and GAA codons is impaired in the absence of URM1- and ELP-dependent tRNA modifications. Moreover, in vitro experiments using native tRNAs demonstrate that both modifications enhance binding of tK(UUU) to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content."],["dc.identifier.doi","10.1073/pnas.1300781110"],["dc.identifier.pmid","23836657"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11843"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1091-6490"],["dc.title","tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","17031"],["dc.bibliographiccitation.issue","45"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","17038"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Mittelstaet, Joerg"],["dc.contributor.author","Konevega, Andrey L."],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2018-01-26T06:48:27Z"],["dc.date.available","2018-01-26T06:48:27Z"],["dc.date.issued","2013"],["dc.description.abstract","Improving the yield of unnatural amino acid incorporation is an important challenge in producing novel designer proteins with unique chemical properties. Here we examine the mechanisms that restrict the incorporation of the fluorescent unnatural amino acid εNH2-Bodipy576/589-lysine (BOP-Lys) into a model protein. While the delivery of BOP-Lys-tRNA(Lys) to the ribosome is limited by its poor binding to elongation factor Tu (EF-Tu), the yield of incorporation into peptide is additionally controlled at the step of BOP-Lys-tRNA release from EF-Tu into the ribosome. The unnatural amino acid appears to disrupt the interactions that balance the strength of tRNA binding to EF-Tu-GTP with the velocity of tRNA dissociation from EF-Tu-GDP on the ribosome, which ensure uniform incorporation of standard amino acids. Circumventing this potential quality control checkpoint that specifically prevents incorporation of unnatural amino acids into proteins may provide a new strategy to increase yields of unnatural polymers."],["dc.identifier.doi","10.1021/ja407511q"],["dc.identifier.pmid","24079513"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11837"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1520-5126"],["dc.title","A kinetic safety gate controlling the delivery of unnatural amino acids to the ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]