Different regions of the class P-III snake venom metalloproteinasejararhagin are involved in binding to a2b1 integrin and collagen
Toxicon
; 55(6): 1093-1099, Jan 28, 2010.
Artigo
em Inglês
| Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO
| ID: biblio-1068251
Biblioteca responsável:
BR78.1
Localização: BR78.1
ABSTRACT
SVMPs are multi-domain proteolytic enzymes in which disintegrin-like and cysteine-rich domains bind to cell receptors, plasma or ECM proteins. We have recently reported thatjararhagin, a P-III class SVMP, binds to collagen with high affinity through an epitope located within the Da-disintegrin sub-domain. In this study, we evaluated the binding of jararhagin to a2b1 integrin (collagen receptor) using monoclonal antibodies and recombinant jararhagin fragments. In solid phase assays, binding of jararhagin to a2b1 integrin was detectable from concentrations of 20 nM. Using recombinant fragments of jararhagin, only fragment JC76 (residues 344421), showed a significant binding to recombinant a2b1 integrin. The anti-jararhagin monoclonal antibody MAJar 3 efficiently neutralised binding ofjararhagin to collagen, but not to recombinant a2b1 integrin nor to cell-surface-exposed a2b1 integrin (a2-K562 transfected cells and platelets). The same antibody neutralised collagen-induced platelet aggregation. Our data suggest that jararhagin binding to collagen and a2b1 integrin occurs by two independent motifs, which are located on disintegrin-like and cysteine-rich domains, respectively. Moreover, toxin binding to collagen appears to be sufficient to inhibit collagen-induced platelet aggregation.
Buscar no Google
Coleções:
Bases de dados nacionais
/
Brasil
Base de dados:
Sec. Est. Saúde SP
/
SESSP-IBACERVO
/
SESSP-IBPROD
Assunto principal:
Venenos de Serpentes
Limite:
Animais
Idioma:
Inglês
Revista:
Toxicon
Ano de publicação:
2010
Tipo de documento:
Artigo
Instituição/País de afiliação:
Instituto Butantan/BR