The structure of p85ni in class IA phosphoinositide 3-kinase exhibits interdomain disorder.
Biochemistry
; 49(10): 2159-66, 2010 Mar 16.
Article
em En
| MEDLINE
| ID: mdl-20131869
ABSTRACT
Regulation of the class IA PI 3-kinase involves inhibition and stabilization of the catalytic subunit (p110) by the regulatory subunit (p85). Regulation is achieved by two major contacts a stable interface involving the adapter-binding domain (ABD) of p110 and the inter-SH2 (iSH2) domain of p85 and a regulatory interaction between the N-terminal SH2 (nSH2) domain of p85 and the helical domain of p110. In the present study, we have examined the relative orientation of the nSH2 and iSH2 of p85alpha using site-directed spin labeling and pulsed EPR. Surprisingly, both distance measurements and distance distributions suggest that the nSH2 domain is highly disordered relative to the iSH2 domain. Molecular modeling based on EPR distance restraints suggests that the nSH2 domain moves in a hinge-like manner, sampling a torus space around the proximal end of the iSH2 domain. These data have important implications for the mechanism by which p85/p110 dimers are regulated by phosphopeptides.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Domínios de Homologia de src
/
Fosfatidilinositol 3-Quinases
Tipo de estudo:
Health_economic_evaluation
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos