The Adaptive Potential of the Middle Domain of Yeast Hsp90 Article Swipe
YOU?
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· 2020
· Open Access
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· DOI: https://doi.org/10.1093/molbev/msaa211
The 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.
Related Topics
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/molbev/msaa211
- https://academic.oup.com/mbe/article-pdf/38/2/368/36084529/msaa211.pdf
- OA Status
- hybrid
- Cited By
- 11
- References
- 69
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3082826065
Raw OpenAlex JSON
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https://openalex.org/W3082826065Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/molbev/msaa211Digital Object Identifier
- Title
-
The Adaptive Potential of the Middle Domain of Yeast Hsp90Work title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2020Year of publication
- Publication date
-
2020-08-29Full publication date if available
- Authors
-
Pamela A. Cote-Hammarlof, Inês Fragata, Julia M. Flynn, David Mavor, Konstantin B. Zeldovich, Claudia Bank, Daniel N. BolonList of authors in order
- Landing page
-
https://doi.org/10.1093/molbev/msaa211Publisher landing page
- PDF URL
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https://academic.oup.com/mbe/article-pdf/38/2/368/36084529/msaa211.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
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https://academic.oup.com/mbe/article-pdf/38/2/368/36084529/msaa211.pdfDirect OA link when available
- Concepts
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Biology, Allosteric regulation, Adaptation (eye), Hsp90, Genetics, Chaperone (clinical), Gene, Heat shock protein, Mutation, Amino acid, Computational biology, Evolutionary biology, Receptor, Neuroscience, Medicine, PathologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
11Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 2, 2023: 3, 2022: 5, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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69Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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