Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control.
Arch Biochem Biophys
; 494(2): 216-25, 2010 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-20005866
ABSTRACT
Allostery has evolved as a form of local communication between interacting protein partners allowing them to quickly sense changes in their immediate vicinity in response to external cues. Herein, using isothermal titration calorimetry (ITC) in conjunction with circular dichroism (CD) and macromolecular modeling (MM), we show that the binding of Grb2 adaptor--a key signaling molecule involved in the activation of Ras GTPase--to its downstream partners Sos1 guanine nucleotide exchange factor and Gab1 docker is under tight allosteric regulation. Specifically, our findings reveal that the binding of one molecule of Sos1 to the nSH3 domain allosterically induces a conformational change within Grb2 such that the loading of a second molecule of Sos1 onto the cSH3 domain is blocked and, in so doing, allows Gab1 access to the cSH3 domain in an exclusively non-competitive manner to generate the Sos1-Grb2-Gab1 ternary signaling complex.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Proteína SOS1
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteína Adaptadora GRB2
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Arch Biochem Biophys
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos