title: Functional diversification and specialization of cytosolic 70-kDa heat shock proteins.
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.
authors: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, California State University, Fullerton, Fullerton, CA 92834.
authors: Chelsea
authors: C
authors: McCallister
authors: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, California State University, Fullerton, Fullerton, CA 92834.
authors: Matthew C
authors: MC
authors: Siracusa
authors: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, California State University, Fullerton, Fullerton, CA 92834.
authors: Farzaneh
authors: F
authors: Shirazi
authors: Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA.
authors: Dimitra
authors: D
authors: Chalkia
authors: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, California State University, Fullerton, Fullerton, CA 92834.
authors: Nikolas
authors: N
authors: Nikolaidis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D006360:Heat-Shock Proteins