Interaction of HSPA5 (Grp78, BIP) with negatively charged phospholipid membranes via oligomerization involving the N-terminal end domain

Author(s)

Dores-Silva, Paulo Roberto ^{[1, 2]} ; Cauvi, David M. ^[2] ; Coto, Amanda L. S. ^[1] ; Kiraly, Vanessa T. R. ^[1] ; Borges, Julio C. ^[1] ; De Maio, Antonio ^{[3, 2]}

Affiliation

^[1] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Paulo - Brazil

^[2] Univ Calif San Diego, Sch Med, Dept Surg, Div Trauma Crit Care Burns & Acute Care Surg, La Jolla, CA 92093 - USA

^[3] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 - USA

• Document type: Journal article
• Source: CELL STRESS & CHAPERONES; v. 25, n. 6 JUL 2020.
• Web of Science Citations: 2

Abstract

Heat shock proteins (HSPs) are ubiquitous polypeptides expressed in all living organisms that participate in several basic cellular processes, including protein folding, from which their denomination as molecular chaperones originated. There are several HSPs, including HSPA5, also known as 78-kDa glucose-regulated protein (GRP78) or binding immunoglobulin protein (BIP) that is an ER resident involved in the folding of polypeptides during their translocation into this compartment prior to the transition to the Golgi network. HSPA5 is detected on the surface of cells or secreted into the extracellular environment. Surface HSPA5 has been proposed to have various roles, such as receptor-mediated signal transduction, a co-receptor for soluble ligands, as well as a participant in tumor survival, proliferation, and resistance. Recently, surface HSPA5 has been reported to be a potential receptor of some viruses, including the novel SARS-CoV-2. In spite of these observations, the association of HSPA5 within the plasma membrane is still unclear. To gain information about this process, we studied the interaction of HSPA5 with liposomes made of different phospholipids. We found that HSPA5 has a high affinity for negatively charged phospholipids, such as palmitoyl-oleoyl phosphoserine (POPS) and cardiolipin (CL). The N-terminal and C-terminal domains of HSPA5 were independently capable of interacting with negatively charged phospholipids, but to a lesser extent than the full-length protein, suggesting that both domains are required for the maximum insertion into membranes. Interestingly, we found that the interaction of HSPA5 with negatively charged liposomes promotes an oligomerization process via intermolecular disulfide bonds in which the N-terminus end of the protein plays a critical role. (AU)

• FAPESP's process: 14/16646-0 - Human mortalin: interaction with co-chaperones, p53 and mutants, aggregation kinectics, regulation/modulation and vesicle secretion
• Grantee: Paulo Roberto das Dores da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/22477-1 - Human mortalin: interaction with liposomes, mitochondrion membrane, beta-amyloids and effect of their presence in the toxicity of beta-amyloids on neurons
• Grantee: Paulo Roberto das Dores da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 17/07335-9 - Studies of human HSP70 isoforms residing in the cytoplasm and mitochondria and their high molecular weight oligomers: interaction with co-chaperones and client proteins
• Grantee: Julio Cesar Borges
• Support Opportunities: Regular Research Grants