Structural insights into blood coagulation factor VIII: Procoagulant complexes, membrane binding, and antibody inhibition.
J Thromb Haemost
; 20(9): 1957-1970, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35722946
ABSTRACT
Advances in structural studies of blood coagulation factor VIII (FVIII) have provided unique insight into FVIII biochemistry. Atomic detail models of the B domain-deleted FVIII structure alone and in complex with its circulatory partner, von Willebrand factor (VWF), provide a structure-based rationale for hemophilia A-associated mutations which impair FVIII stability and increase FVIII clearance rates. In this review, we discuss the findings from these studies and their implications toward the design of a recombinant FVIII with improved circulatory half-life. Additionally, we highlight recent structural studies of FVIII bound to inhibitory antibodies that have refined our understanding of FVIII binding to activated platelet membranes and formation of the intrinsic tenase complex. The combination of bioengineering and structural efforts to understand FVIII biochemistry will improve therapeutics for treating hemophilia A, either through FVIII replacement therapeutics, immune tolerance induction, or gene therapy approaches.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator VIII
/
Hemofilia A
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos