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The Adaptive Potential of the Middle Domain of Yeast Hsp90

2021-02Journal article Open access
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dc.contributor.authorCote-Hammarlof, Pamela, A.
dc.contributor.authorDe mendonça fragata almeida, Inês
dc.contributor.authorFlynn, Julia
dc.contributor.authorMavor, David
dc.contributor.authorZeldovich, Konstantin
dc.contributor.authorBank, Claudia
dc.contributor.authorBolon, Daniel N.A.
dc.date.accessioned2021-02-26T16:07:59Z
dc.date.available2021-02-26T16:07:59Z
dc.date.issued2021-02
dc.description.abstractThe distribution of fitness effects (DFEs) of new mutations across different environments quantifies the potential for adaptation in a given environment and its cost in others. So far, results regarding the cost of adaptation across environments have been mixed, and most studies have sampled random mutations across different genes. Here, we quantify systematically how costs of adaptation vary along a large stretch of protein sequence by studying the distribution of fitness effects of the same ≈2,300 amino-acid changing mutations obtained from deep mutational scanning of 119 amino acids in the middle domain of the heat shock protein Hsp90 in five environments. This region is known to be important for client binding, stabilization of the Hsp90 dimer, stabilization of the N-terminal-Middle and Middle-C-terminal interdomains, and regulation of ATPase–chaperone activity. Interestingly, we find that fitness correlates well across diverse stressful environments, with the exception of one environment, diamide. Consistent with this result, we find little cost of adaptation; on average only one in seven beneficial mutations is deleterious in another environment. We identify a hotspot of beneficial mutations in a region of the protein that is located within an allosteric center. The identified protein regions that are enriched in beneficial, deleterious, and costly mutations coincide with residues that are involved in the stabilization of Hsp90 interdomains and stabilization of client-binding interfaces, or residues that are involved in ATPase–chaperone activity of Hsp90. Thus, our study yields information regarding the role and adaptive potential of a protein sequence that complements and extends known structural information.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPamela A Cote-Hammarlof, Inês Fragata, Julia Flynn, David Mavor, Konstantin B Zeldovich, Claudia Bank, Daniel N A Bolon, The Adaptive Potential of the Middle Domain of Yeast Hsp90, Molecular Biology and Evolution, Volume 38, Issue 2, February 2021, Pages 368–379,pt_PT
dc.identifier.doihttps://doi.org/10.1093/molbev/msaa211pt_PT
dc.identifier.urihttp://hdl.handle.net/10451/46548
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford Academic Presspt_PT
dc.relationR01GM112844 from the National Institutes of Healthpt_PT
dc.relationJPIAMR/0001/2016 from FCTpt_PT
dc.relationEMBO Installation Grant IG4152pt_PT
dc.relationERC Starting Grant 804569—FIT2GOpt_PT
dc.relation.publisherversionhttps://academic.oup.com/mbe/article/38/2/368/5900269pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectadaptationpt_PT
dc.subjectchaperonept_PT
dc.subjectfitness effectspt_PT
dc.subjectmutationspt_PT
dc.subjectdeep mutational scanningpt_PT
dc.titleThe Adaptive Potential of the Middle Domain of Yeast Hsp90pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceOxfordpt_PT
oaire.citation.endPage379pt_PT
oaire.citation.startPage368pt_PT
oaire.citation.titleMolecular Biology and Evolutionpt_PT
oaire.citation.volume38pt_PT
person.familyNameLopes de Mendonça Fragata Almeida
person.givenNameInês Regina
person.identifierResearcherID: I-9876-2014
person.identifier.ciencia-idF812-23C0-FEC5
person.identifier.orcid0000-0001-6865-1510
person.identifier.scopus-author-id24474345000
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication56a3ed3e-c763-4ecc-855d-2ac479a1585b
relation.isAuthorOfPublication.latestForDiscovery56a3ed3e-c763-4ecc-855d-2ac479a1585b

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