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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Determinantes estructurales para la inhibición inducida por GoLoco de la liberación de nucleótidos por las
Randall J Kimple1, Michelle E Kimple, Laurie Betts
1Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Nature
|April 27, 2002
Resumen
Las proteínas reguladoras con el motivo GoLoco se unen a las subunidades Galpha, manteniendo la disociación de la proteína G. El análisis estructural revela interacciones clave, incluida la tríada GoLoco.
Área de la Ciencia:
- Biología molecular La biología molecular.
- Biología estructural Biología estructural.
- La señalización celular de las células.
Sus antecedentes:
- Las G-proteínas heterotriméricas median la señalización de los receptores de la superficie celular.
- La activación de la proteína G implica la unión y disociación de la subunidad Galpha a la GTP.
Objetivo del estudio:
- Para aclarar la base estructural de la regulación de la proteína G mediada por el motivo GoLoco.
- Para entender cómo las proteínas GoLoco interactúan con las subunidades Galpha.
Principales métodos:
- Cristalografía de rayos X de Galpha ((i1) PIB ligado a RGS14 región de GoLoco.
- Experimentos de intercambio de dominio.
Principales resultados:
- Contactos estructurales detallados entre el motivo GoLoco y Galpha (i1) PIB.
- Identificación del papel de la tríada Asp/Glu-Gln-Arg conservada en la interacción del bolsillo de unión de nucleótidos.
- La evidencia de que el dominio totalmente helicoidal de Galpha y los residuos C-terminales dictan la especificidad de GoLoco.
Conclusiones:
- El motivo GoLoco interactúa directamente con las subunidades Galpha para regular la señalización de la proteína G.
- Las ideas estructurales proporcionan una base para comprender la regulación de la proteína G por las proteínas RGS.
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