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

Scientific Reports
Chelsea McCallisterNikolas Nikolaidis

Abstract

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.

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Citations

Mar 1, 2016·Biochemical and Biophysical Research Communications·Chelsea McCallisterNikolas Nikolaidis
Sep 8, 2015·Cell Stress & Chaperones·Chelsea McCallisterNikolas Nikolaidis
Oct 18, 2015·Biochemical and Biophysical Research Communications·Chelsea McCallisterNikolas Nikolaidis
Aug 23, 2020·International Journal of Molecular Sciences·Larissa SmuldersNikolas Nikolaidis
Dec 24, 2020·International Journal of Molecular Sciences·Peter NguyenNikolas Nikolaidis
Nov 6, 2018·Biochemical and Biophysical Research Communications·Ryan OliverioNikolas Nikolaidis

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Datasets Mentioned

BETA
BC054782
BC089457

Methods Mentioned

BETA
protein folding
Protein Assay
electrophoresis
light scattering

Software Mentioned

DaliLite
SigmaPlot
BioEdit
BLAST
MAFFT
Pymol
PBEQ Solver
MEGA
Systat

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