Human heat shock cognate protein (HSC70/HSPA8) interacts with negatively charged phospholipids by a different mechanism than other HSP70s and brings HSP90 into membranes

Cell Stress Chaperones. 2021 Jul;26(4):671-684. doi: 10.1007/s12192-021-01210-8. Epub 2021 May 18.

Abstract

Heat shock proteins (HSP) are critical elements for the preservation of cellular homeostasis by participating in an array of biological processes. In addition, HSP play an important role in cellular protection from various environmental stresses. HSP are part of a large family of different molecular mass polypeptides, displaying various expression patterns, subcellular localizations, and diversity functions. An unexpected observation was the detection of HSP on the cell surface. Subsequent studies have demonstrated that HSP have the ability to interact and penetrate lipid bilayers by a process initiated by the recognition of phospholipid heads, followed by conformational changes, membrane insertion, and oligomerization. In the present study, we described the interaction of HSPA8 (HSC70), the constitutive cytosolic member of the HSP70 family, with lipid membranes. HSPA8 showed high selectivity for negatively charged phospholipids, such as phosphatidylserine and cardiolipin, and low affinity for phosphatidylcholine. Membrane insertion was mediated by a spontaneous process driven by increases in entropy and diminished by the presence of ADP or ATP. Finally, HSPA8 was capable of driving into the lipid bilayer HSP90 that does not display any lipid biding capacity by itself. This observation suggests that HSPA8 may act as a membrane chaperone.

Keywords: Chaperones; HSP90AA1; HSPA1A; HSPA8; Hsp70; Liposomes; Membranes; Phospholipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiolipins / metabolism
  • Cell Membrane / metabolism
  • HSC70 Heat-Shock Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Response / drug effects
  • Heat-Shock Response / physiology
  • Humans
  • Liposomes / metabolism
  • Molecular Chaperones / metabolism
  • Phospholipids / metabolism*

Substances

  • Cardiolipins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • HSPA8 protein, human
  • Heat-Shock Proteins
  • Liposomes
  • Molecular Chaperones
  • Phospholipids