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Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting.
Mavor, David; Barlow, Kyle; Thompson, Samuel; Barad, Benjamin A; Bonny, Alain R; Cario, Clinton L; Gaskins, Garrett; Liu, Zairan; Deming, Laura; Axen, Seth D; Caceres, Elena; Chen, Weilin; Cuesta, Adolfo; Gate, Rachel E; Green, Evan M; Hulce, Kaitlin R; Ji, Weiyue; Kenner, Lillian R; Mensa, Bruk; Morinishi, Leanna S; Moss, Steven M; Mravic, Marco; Muir, Ryan K; Niekamp, Stefan; Nnadi, Chimno I; Palovcak, Eugene; Poss, Erin M; Ross, Tyler D; Salcedo, Eugenia C; See, Stephanie K; Subramaniam, Meena; Wong, Allison W; Li, Jennifer; Thorn, Kurt S; Conchúir, Shane Ó; Roscoe, Benjamin P; Chow, Eric D; DeRisi, Joseph L; Kortemme, Tanja; Bolon, Daniel N; Fraser, James S.
Affiliation
  • Mavor D; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Barlow K; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Thompson S; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Barad BA; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Bonny AR; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Cario CL; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Gaskins G; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Liu Z; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Deming L; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
  • Axen SD; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Caceres E; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Chen W; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Cuesta A; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Gate RE; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Green EM; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Hulce KR; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Ji W; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Kenner LR; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Mensa B; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Morinishi LS; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Moss SM; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Mravic M; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Muir RK; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Niekamp S; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Nnadi CI; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Palovcak E; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Poss EM; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Ross TD; Biophysics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Salcedo EC; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • See SK; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Subramaniam M; Bioinformatics Graduate Group, University of California, San Francisco, San Francisco, United States.
  • Wong AW; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
  • Li J; UCSF Science and Health Education Partnership, University of California, San Francisco, San Francisco, United States.
  • Thorn KS; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
  • Conchúir SÓ; Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biology, University of California, San Francisco, San Francisco, United States.
  • Roscoe BP; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
  • Chow ED; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
  • DeRisi JL; Center for Advanced Technology, University of California, San Francisco, San Francisco, United States.
  • Kortemme T; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
  • Bolon DN; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
  • Fraser JS; Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biology, University of California, San Francisco, San Francisco, United States.
Elife ; 52016 04 25.
Article de En | MEDLINE | ID: mdl-27111525
ABSTRACT
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.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Saccharomyces cerevisiae / Stress physiologique / Analyse de mutations d'ADN / Ubiquitine / Protéines mutantes Type d'étude: Prognostic_studies Limites: Humans Langue: En Journal: Elife Année: 2016 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Saccharomyces cerevisiae / Stress physiologique / Analyse de mutations d'ADN / Ubiquitine / Protéines mutantes Type d'étude: Prognostic_studies Limites: Humans Langue: En Journal: Elife Année: 2016 Type de document: Article Pays d'affiliation: États-Unis d'Amérique