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dc.contributor.authorBershtein, Shimon
dc.contributor.authorMu, Wanmeng
dc.contributor.authorSerohijos, Adrian
dc.contributor.authorZhou, Jingwen
dc.contributor.authorShakhnovich, Eugene Isaacovitch
dc.date.accessioned2014-09-02T13:02:49Z
dc.date.issued2012
dc.identifier.citationBershtein, Shimon, Wanmeng Mu, Adrian W.R. Serohijos, Jingwen Zhou, and Eugene I. Shakhnovich. 2012. Protein Quality Control Acts on Folding Intermediates to Shape the Effects of Mutations on Organismal Fitness. Molecular Cell 49, no. 1: 133–144.en_US
dc.identifier.issn1097-2765en_US
dc.identifier.issn1097-4164en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12763605
dc.description.abstractWhat are the molecular properties of proteins that fall on the radar of protein quality control (PQC)? Here we mutate the E. coli’s gene encoding dihydrofolate reductase (DHFR) and replace it with bacterial orthologous genes to determine how components of PQC modulate fitness effects of these genetic changes. We find that chaperonins GroEL/ES and protease Lon compete for binding to molten globule intermediate of DHFR, resulting in a peculiar symmetry in their action: overexpression of GroEL/ES and deletion of Lon both restore growth of deleterious DHFR mutants and most of the slow-growing orthologous DHFR strains. Kinetic steady-state modeling predicts and experimentation verifies that mutations affect fitness by shifting the flux balance in cellular milieu between protein production, folding, and degradation orchestrated by PQC through the interaction with folding intermediates.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.molcel.2012.11.004en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545112/en_US
dc.relation.hasversionhttp://www.people.fas.harvard.edu/~serohij/pdf/bmss_molecularcell2013.pdfen_US
dash.licenseLAA
dc.titleProtein Quality Control Acts on Folding Intermediates to Shape the Effects of Mutations on Organismal Fitnessen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalMolecular Cellen_US
dash.depositing.authorShakhnovich, Eugene Isaacovitch
dash.waiver2012-11-02
dc.date.available2014-09-02T13:02:49Z
dc.identifier.doi10.1016/j.molcel.2012.11.004*
workflow.legacycommentsFrom Waiver Table Can post manuscript per sherpaen_US
dash.contributor.affiliatedBershtein, Shimon
dash.contributor.affiliatedSerohijos, Adrian
dash.contributor.affiliatedShakhnovich, Eugene


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