The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch.
Mol Cell
; 32(4): 564-75, 2008 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-19026786
ABSTRACT
PH domains, by binding to phosphoinositides, often serve as membrane-targeting modules. Using crystallographic, biochemical, and cell biological approaches, we have uncovered a mechanism that the integrin-signaling adaptor Skap-hom uses to mediate cytoskeletal interactions. Skap-hom is a homodimer containing an N-terminal four-helix bundle dimerization domain, against which its two PH domains pack in a conformation incompatible with phosphoinositide binding. The isolated PH domains bind PI[3,4,5]P(3), and mutations targeting the dimerization domain or the PH domain's PI[3,4,5]P(3)-binding pocket prevent Skap-hom localization to ruffles. Targeting is retained when the PH domain is deleted or by combined mutation of the PI[3,4,5]P(3)-binding pocket and the PH/dimerization domain interface. Thus, the dimerization and PH domain form a PI[3,4,5]P(3)-responsive molecular switch that controls Skap-hom function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositóis
/
Proteínas Adaptadoras de Transdução de Sinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article