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Membranotropic and biological activities of the membrane fusion peptides from SARS-CoV spike glycoprotein: The importance of the complete internal fusion peptide domain.
Basso, Luis Guilherme Mansor; Zeraik, Ana Eliza; Felizatti, Ana Paula; Costa-Filho, Antonio José.
  • Basso LGM; Laboratório de Ciências Físicas, Centro de Ciência e Tecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, 28013-602 Campos dos Goytacazes, RJ, Brazil; Laboratório de Biofísica Molecular, Departamento de Física, Faculdade de Filosofia, Ciências e Letras d
  • Zeraik AE; Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, 28013-602 Campos dos Goytacazes, RJ, Brazil; Grupo de Biofísica e Biologia Estrutural "Sérgio Mascarenhas", Institut
  • Felizatti AP; Laboratório de Produtos Naturais, Departamento de Química, Centro de Ciências Exatas e de Tecnologia, Universidade Federal de São Carlos, Rod. Washington Luiz, Km 235, Monjolinho, 13565905, São Carlos, SP, Brazil; Grupo de Biofísica e Biologia Estrutural "Sérgio Mascarenhas", Instituto de Física de
  • Costa-Filho AJ; Laboratório de Biofísica Molecular, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, 14040-901 Ribeirão Preto, SP, Brazil. Electronic address: ajcosta@usp.br.
Biochim Biophys Acta Biomembr ; 1863(11): 183697, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1316392
ABSTRACT
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 α-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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phospholipids / Erythrocyte Membrane / Spike Glycoprotein, Coronavirus Limits: Humans Language: English Journal: Biochim Biophys Acta Biomembr Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phospholipids / Erythrocyte Membrane / Spike Glycoprotein, Coronavirus Limits: Humans Language: English Journal: Biochim Biophys Acta Biomembr Year: 2021 Document Type: Article