title: HspA1A, a 70-kDa heat shock protein, differentially interacts with anionic lipids.
abstract: HspA1A, a 70-kDa heat shock protein, binds to specific lipids. This interaction allows HspA1A to associate with the plasma and other cellular membranes, where it regulates many vital functions like immunity, membrane stabilization, autophagy, and apoptosis. However, the molecular mechanism of the HspA1A-lipid interactions has yet to be fully characterized. Therefore, in this study, we characterized the interaction of HspA1A with three lipids, bis-(monoacylglycero)-phosphate, cardiolipin, and sulfatide. Our results revealed that, first, HspA1A embeds in membranes when bound to liposomes composed of cardiolipin and sulfatide. Second, the binding of HspA1A to lipids is complex and although important, electrostatic interactions alone cannot fully explain the observed binding. Third, the two HspA1A domains, the nucleotide-binding domain and the substrate-binding domain, differentially bind to lipids in a lipid-specific manner. Fourth, HspA1A lipid-binding is reduced by the presence of nucleotides, but it is unaffected by the presence of a peptide-substrate. These observations suggest that HspA1A binds to lipids via a multi-step mechanism and this interaction depends on the specific physicochemical properties of the lipid. We speculate that the association of HspA1A with lipids like the mitochondrial cardiolipin, which is an organelle marker, may facilitate the translocation and localized function of the molecular chaperone to particular sub-cellular compartments.
authors.affiliation: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Applied Mathematics, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA, 92834-6850, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: McCallister
authors.affiliation: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Applied Mathematics, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA, 92834-6850, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Kdeiss
authors.affiliation: Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Applied Mathematics, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA, 92834-6850, USA. Electronic address: nnikolaidis@fullerton.edu.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Nikolaidis
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000838:Anions; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008246:Lysophospholipids / Q000737:chemistry* / Q000378:metabolism; D050178:Monoglycerides / Q000737:chemistry* / Q000378:metabolism; D011189:Potassium Chloride / Q000737:chemistry; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013433:Sulfoglycosphingolipids / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000838:Anions; D002308:Cardiolipins; D018840:HSP70 Heat-Shock Proteins; C498550:Hsp70.3 protein, mouse; D008051:Lipid Bilayers; D008081:Liposomes; D008246:Lysophospholipids; D050178:Monoglycerides; D013433:Sulfoglycosphingolipids; C012786:bis(monoacylglyceryl)phosphate; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Heat-shock proteins; Lipid-binding; Liposomes; Membranes; Stress