Differences in intradomain and interdomain motion confer distinct activation properties to structurally similar Gα proteins.
Proc Natl Acad Sci U S A
; 109(19): 7275-9, 2012 May 08.
Article
em En
| MEDLINE
| ID: mdl-22529365
ABSTRACT
Proteins with similar crystal structures can have dissimilar rates of substrate binding and catalysis. Here we used molecular dynamics simulations and biochemical analysis to determine the role of intradomain and interdomain motions in conferring distinct activation rates to two Gα proteins, Gα(i1) and GPA1. Despite high structural similarity, GPA1 can activate itself without a receptor, whereas Gα(i1) cannot. We found that motions in these proteins vary greatly in type and frequency. Whereas motion is greatest in the Ras domain of Gα(i1), it is greatest in helices αA and αB from the helical domain of GPA1. Using protein chimeras, we show that helix αA from GPA1 is sufficient to confer rapid activation to Gα(i1). Gα(i1) has less intradomain motion than GPA1 and instead displays interdomain displacement resembling that observed in a receptor-heterotrimer crystal complex. Thus, structurally similar proteins can have distinct atomic motions that confer distinct activation mechanisms.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estrutura Terciária de Proteína
/
Estrutura Secundária de Proteína
/
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
/
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos