Functional diversification and specialization of cytosolic 70-kDa heat shock proteins

A fundamental question in molecular evolution is how protein functional differentiation alters the ability of cells and organisms to cope with stress and survive. To answer this question we used two paralogous Hsp70s from mouse and explored whether these highly similar cytosolic molecular chaperones...

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Bibliographic Details
Published in:Scientific reports 2015-03, Vol.5 (1), p.9363-9363, Article 9363
Main Authors: McCallister, Chelsea, Siracusa, Matthew C, Shirazi, Farzaneh, Chalkia, Dimitra, Nikolaidis, Nikolas
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell death
Cell survival
Cellular stress response
Chaperones
Cytosol - metabolism
Heat shock proteins
Heat-Shock Proteins - chemistry
Heat-Shock Proteins - classification
Heat-Shock Proteins - metabolism
Lipids
Mice
Molecular evolution
Molecular Sequence Data
Phylogeny
Proteins
Sequence Homology, Amino Acid
Specialization
Survival
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Summary:A fundamental question in molecular evolution is how protein functional differentiation alters the ability of cells and organisms to cope with stress and survive. To answer this question we used two paralogous Hsp70s from mouse and explored whether these highly similar cytosolic molecular chaperones, which apart their temporal expression have been considered functionally interchangeable, are differentiated with respect to their lipid-binding function. We demonstrate that the two proteins bind to diverse lipids with different affinities and therefore are functionally specialized. The observed lipid-binding patterns may be related with the ability of both Hsp70s to induce cell death by binding to a particular plasma-membrane lipid, and the potential of only one of them to promote cell survival by binding to a specific lysosomal-membrane lipid. These observations reveal that two seemingly identical proteins differentially modulate cellular adaptation and survival by having acquired specialized functions via sequence divergence. Therefore, this study provides an evolutionary paradigm, where promiscuity, specificity, sub- and neo-functionalization orchestrate one of the most conserved systems in nature, the cellular stress-response.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep09363