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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CELL STRESS & CHAPERONES; v. 25, n. 6 JUL 2020.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 14/16646-0 - Mortalina humana: interação com co-chaperonas, p53 e mutantes, cinética de agregação, regulação/modulação e secreção por vesículas
• Beneficiário: Paulo Roberto das Dores da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/26131-5 - Chaperoma: estudo da relação entre a estrutura dos seus componentes e a manutenção da proteostase
• Beneficiário: Carlos Henrique Inacio Ramos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/50161-8 - Estudo da estrutura e função da chaperona Hsp90 com ênfase no seu papel em homeostase celular
• Beneficiário: Carlos Henrique Inacio Ramos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/22477-1 - Mortalina humana: interação com lipossomos, membrana mitocondrial, beta-amiloides e efeito de sua presença na toxicidade de beta-amiloides em neurônios
• Beneficiário: Paulo Roberto das Dores da Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 17/07335-9 - Estudos das isoformas da HSP70 humana residentes no citoplasma e mitocôndria e de seus oligômeros de alta massa molecular: interação com co-chaperonas e proteínas clientes
• Beneficiário: Julio Cesar Borges
• Modalidade de apoio: Auxílio à Pesquisa - Regular