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dc.contributor.authorMavor, David
dc.contributor.authorRoscoe, Benjamin P.
dc.contributor.authorBolon, Daniel N.
dc.contributor.authorFraser, James S.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:42:14Z
dc.date.available2022-08-23T16:42:14Z
dc.date.issued2016-04-25
dc.date.submitted2016-08-16
dc.identifier.citation<p>Elife. 2016 Apr 25;5. pii: e15802. doi: 10.7554/eLife.15802. <a href="http://dx.doi.org/10.7554/eLife.15802">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.15802
dc.identifier.pmid27111525
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40049
dc.description<p>Full author list omitted for brevity. For full list of authors see article.</p>
dc.description.abstractUbiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that this tolerance would be reduced by chemically induced physiologic perturbations. To test this hypothesis, a class of first year UCSF graduate students employed deep mutational scanning to determine the fitness landscape of all possible single residue mutations in the presence of five different small molecule perturbations. These perturbations uncover 'shared sensitized positions' localized to areas around the hydrophobic patch and the C-terminus. In addition, we identified perturbation specific effects such as a sensitization of His68 in HU and a tolerance to mutation at Lys63 in DTT. Our data show how chemical stresses can reduce buffering effects in the ubiquitin proteasome system. Finally, this study demonstrates the potential of lab-based interdisciplinary graduate curriculum.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27111525&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2016, Mavor et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectS. cerevisiae
dc.subjectbiophysics
dc.subjectchemical biology
dc.subjectcomputational biology
dc.subjectdeep mutational scanning
dc.subjectevolutionary biology
dc.subjectgenomics
dc.subjectproteasome
dc.subjectproteostasis
dc.subjectsystems biology
dc.subjectubiquitin
dc.subjectBiochemistry
dc.subjectBiophysics
dc.subjectComputational Biology
dc.subjectGenomics
dc.subjectOther Ecology and Evolutionary Biology
dc.subjectSystems Biology
dc.titleDetermination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting
dc.typeJournal Article
dc.source.journaltitleeLife
dc.source.volume5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3859&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2854
dc.identifier.contextkey8985400
refterms.dateFOA2022-08-23T16:42:14Z
html.description.abstract<p>Ubiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that this tolerance would be reduced by chemically induced physiologic perturbations. To test this hypothesis, a class of first year UCSF graduate students employed deep mutational scanning to determine the fitness landscape of all possible single residue mutations in the presence of five different small molecule perturbations. These perturbations uncover 'shared sensitized positions' localized to areas around the hydrophobic patch and the C-terminus. In addition, we identified perturbation specific effects such as a sensitization of His68 in HU and a tolerance to mutation at Lys63 in DTT. Our data show how chemical stresses can reduce buffering effects in the ubiquitin proteasome system. Finally, this study demonstrates the potential of lab-based interdisciplinary graduate curriculum.</p>
dc.identifier.submissionpathoapubs/2854
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pagese15802


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Copyright © 2016, Mavor et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2016, Mavor et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.