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NS1 from Two Zika Virus Strains Differently Interact with a Membrane: Insights to Understand Their Differential Virulence.
Poveda Cuevas, Sergio Alejandro; Barroso da Silva, Fernando L; Etchebest, Catherine.
Afiliação
  • Poveda Cuevas SA; Programa Interunidades em Bioinformática, Universidade de São Paulo, Rua do Matão, 1010, São Paulo, São Paulo BR-05508-090, Brazil.
  • Barroso da Silva FL; Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/no-Campus da USP, Ribeirão Preto, São Paulo BR-14040-903, Brazil.
  • Etchebest C; Goethe University Frankfurt, Institute of Biochemistry II, Theodor-Stern-Kai 7, Frankfurt am Main, Hesse DE-60590, Germany.
J Chem Inf Model ; 63(4): 1386-1400, 2023 02 27.
Article em En | MEDLINE | ID: mdl-36780300
Zika virus (ZIKV) from Uganda (UG) expresses a phenotype related to fetal loss, whereas the variant from Brazil (BR) induces microcephaly in neonates. The differential virulence has a direct relation to biomolecular mechanisms that make one strain more aggressive than the other. The nonstructural protein 1 (NS1) is a key viral toxin to comprehend these viral discrepancies because of its versatility in many processes of the virus life cycle. Here, we aim to examine through coarse-grained models and molecular dynamics simulations the protein-membrane interactions for both NS1ZIKV-UG and NS1ZIKV-BR dimers. A first evaluation allowed us to establish that the NS1 proteins, in the membrane presence, explore new conformational spaces when compared to systems simulated without a lipid bilayer. These events derive from both differential coupling patterns and discrepant binding affinities to the membrane. The N-terminal domain, intertwined loop, and greasy finger proposed previously as binding membrane regions were also computationally confirmed by us. The anchoring sites have aromatic and ionizable residues that manage the assembly of NS1 toward the membrane, especially for the Ugandan variant. Furthermore, in the presence of the membrane, the difference in the dynamic cross-correlation of residues between the two strains is particularly pronounced in the putative epitope regions. This suggests that the protein-membrane interaction induces changes in the distal part related to putative epitopes. Taken together, these results open up new strategies for the treatment of flaviviruses that would specifically target these dynamic differences.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Zika virus / Infecção por Zika virus Limite: Humans Idioma: En Revista: J Chem Inf Model Assunto da revista: INFORMATICA MEDICA / QUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Zika virus / Infecção por Zika virus Limite: Humans Idioma: En Revista: J Chem Inf Model Assunto da revista: INFORMATICA MEDICA / QUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos