Membranotropic and biological activities of the membrane fusion peptides from SARS-CoV spike glycoprotein: The importance of the complete internal fusion peptide domain

Autor(es)

Mansor Basso, Luis Guilherme ^{[1, 2]} ; Zeraik, Ana Eliza ^{[3, 4]} ; Felizatti, Ana Paula ^{[4, 5]} ; Costa-Filho, Antonio Jose ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Norte Fluminense, Ctr Ciencia & Tecnol, Lab Ciencias Fis, Ave Alberto Lamego 2000, BR-28013602 Campos Dos Goytacazes, RJ - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, Lab Biofis Mol, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Univ Estadual Norte Fluminense, Ctr Biociencias & Biotecnol, Lab Quim & Funcao Proteinas & Peptideos, Ave Alberto Lamego 2000, BR-28013602 Campos Dos Goytacazes, RJ - Brazil

^[4] Univ Sao Paulo, Inst Fis Sao Carlos, Grp Biofis & Biol Estrutural Sergio Mascarenhas, Ave Trabalhador Sao Carlense 400, Sao Carlos, SP - Brazil

^[5] Univ Fed Sao Carlos, Ctr Ciencias Exatas & Tecnol, Dept Quim, Lab Prod Nat, Rod Washington Luiz, Km 235, BR-13565905 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1863, n. 11 NOV 1 2021.
• Citações Web of Science: 0

Resumo

Fusion peptides (FP) are prominent hydrophobic segments of viral fusion proteins that play critical roles in viral entry. FPs interact with and insert into the host lipid membranes, triggering conformational changes in the viral protein that leads to the viral-cell fusion. Multiple membrane-active domains from the severe acute respiratory syndrome (SARS) coronavirus (CoV) spike protein have been reported to act as the functional fusion peptide such as the peptide sequence located between the S1/S2 and S2' cleavage sites (FP1), the S2'-adjacent fusion peptide domain (FP2), and the internal FP sequence (cIFP). Using a combined biophysical approach, we demonstrated that the a-helical coiled-coil-forming internal cIFP displayed the highest membrane fusion and permeabilizing activities along with membrane ordering effect in phosphatidylcholine (PC)/phosphatidylglycerol (PG) unilamellar vesicles compared to the other two N-proximal fusion peptide counterparts. While the FP1 sequence displayed intermediate membranotropic activities, the well-conserved FP2 peptide was substantially less effective in promoting fusion, leakage, and membrane ordering in PC/PG model membranes. Furthermore, Ca2+ did not enhance the FP2-induced lipid mixing activity in PC/phosphatidylserine/cholesterol lipid membranes, despite its strong erythrocyte membrane perturbation. Nonetheless, we found that the three putative SARS-CoV membrane-active fusion peptide sequences here studied altered the physical properties of model and erythrocyte membranes to different extents. The importance of the distinct membranotropic and biological activities of all SARS-CoV fusion peptide domains and the pronounced effect of the internal fusion peptide sequence to the whole spike-mediated membrane fusion process are discussed. (AU)

• Processo FAPESP: 08/57910-0 - Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas - INBEQMeDI
• Beneficiário: Richard Charles Garratt
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/50366-7 - Resolving mechanistic details of peptide transport across membranes using crystallographic and non-crystallographic structural biology approaches
• Beneficiário: Antonio José da Costa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/00206-0 - Estrutura e função dos peptídeos de fusão da glicoproteína spike do SARS-CoV
• Beneficiário: Luís Guilherme Mansor Basso
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/18390-5 - Ressonância magnética eletrônica em biofísica molecular: novos e velhos olhares para novos e velhos problemas
• Beneficiário: Antonio José da Costa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular