Molecular View into Preferential Binding of the Factor VII Gla Domain to Phosphatidic Acid.
Biochemistry
; 61(16): 1694-1703, 2022 08 16.
Article
em En
| MEDLINE
| ID: mdl-35853076
ABSTRACT
Factor VII (FVII) is a serine protease with a key role in initiating the coagulation cascade. It is part of a family of vitamin K-dependent clotting proteins, which require vitamin K for formation of their specialized membrane-binding domains (Gla domains). Membrane binding of the FVII Gla domain is critical to the activity of FVII, mediating the formation of its complex with other clotting factors. While Gla domains among coagulation factors are highly conserved in terms of amino acid sequence and structure, they demonstrate differential binding specificity toward anionic lipids. Although most Gla domain-containing clotting proteins display a strong preference for phosphatidylserine (PS), it has been demonstrated that FVII and protein C instead bind preferentially to phosphatidic acid (PA). We have developed the first model of the FVII Gla domain bound to PA lipids in membranes containing PA, the highly mobile membrane mimetic model, which accelerates slow diffusion of lipids in molecular dynamics simulations and therefore facilitates the membrane binding process and enhances sampling of lipid interactions. Simulations were performed using atomic level molecular dynamics, requiring a fixed charge to all atoms. The overall charge assigned to each PA lipid for this study was -1. We also developed an additional model of the FVII Gla domain bound to a 11 PS/PC membrane and compared the modes of binding of PS and PA lipids to FVII, allowing us to identify potential PA-specific binding sites.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Fosfatídicos
/
Fator VII
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA