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Estructura y alostería de la holoenzima tetramérica RIIβ de la PKA
Ping Zhang1, Eric V Smith-Nguyen, Malik M Keshwani
1Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093-0654, USA.
Science (New York, N.Y.)
|February 11, 2012
Resumen
La estructura de la holoenzima adenosina monofosfato cíclico (cAMP) dependiente de la proteína quinasa (PKA) RIIβ(2):C(2) revela cómo la unión al cAMP activa alostericamente el PKA. Esta estructura proporciona información sobre el PKA.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La proteína quinasa dependiente de adenosina monofosfato cíclico (cAMP) (PKA) es una enzima crucial que regula los procesos celulares.
- La PKA existe fisiológicamente como un tetramero que comprende subunidades reguladoras (R) y catalíticas (C).
Objetivo del estudio:
- Determinar la estructura de 2,3 angstroms de la holoenzima PKA tetramérica RIIβ(2):C(2) de longitud completa.
- Para dilucidar el mecanismo de activación alostérica por cAMP a través del análisis estructural.
Principales métodos:
- Cristalografía de rayos X con una resolución de 2.3 angstroms.
- Análisis de la estructura de la holoenzima RIIβ(2):C(2) y de los estados ligados al nucleótido.
Principales resultados:
- La holoenzima RIIβ(2):C(2) forma un dímero de dímeros, revelando una interfaz de anclaje entre las subunidades RIIβ y C.
- La interacción en bucle β4-β5 de la subunidad RIIβ obliga a la subunidad C a una conformación cerrada sin nucleótido.
- Los cristales revelaron productos de reacción (ADP y RIIβ fosforilado) en lugar de ATP, lo que sugiere implicaciones para el ciclo de PKA.
Conclusiones:
- La estructura determinada proporciona una base mecánica para la activación alostérica mediada por cAMP de PKA.
- La estructura cuaternaria del tetramero RIIβ difiere del tetramero RIα, lo que indica distintas disposiciones estructurales entre las isoformas de PKA.
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