Referencia

Nat Struct Mol Biol. 2011 Jan;18(1):14-9.

Autores

Muñoz IG, Yébenes H, Zhou M, Mesa P, Serna M, Park AY, Bragado-Nilsson E, Beloso A, de Cárcer G, Malumbres M, Robinson CV, Valpuesta JM, Montoya G.

Resumen

CCT (chaperonin containing TCP-1, or TRiC) es un oligómero de 1-MDa compuesto de 8 subunidades que forman un doble anillo. En este trabajo se describe la estructura cristalográfica de CCT en complejo con tubulina en una conformación abierta. La estructura sugiere cuál es el mecanismo empleado por la chaperonina para plegar sus sustratos. La organización asimétrica de las subunidades y los nichos de unión de ATP indican que el sustrato es estirado en la cavidad.

Descripción

Protein folding is assisted by molecular chaperones. CCT (chaperonin containing TCP-1, or TRiC) is a 1-MDa oligomer that is built by two rings comprising eight different 60-kDa subunits. This chaperonin regulates the folding of important proteins including actin, α-tubulin and β-tubulin. We used an electron density map at 5.5 Å resolution to reconstruct CCT, which showed a substrate in the inner cavities of both rings. Here we present the crystal structure of the open conformation of this nanomachine in complex with tubulin, providing information about the mechanism by which it aids tubulin folding. The structure showed that the substrate interacts with loops in the apical and equatorial domains of CCT. The organization of the ATP-binding pockets suggests that the substrate is stretched inside the cavity. Our data provide the basis for understanding the function of this chaperonin.


Imágen artículo Marzo
Grupo de Guillermo Montoya (CNIO)


Imágen artículo Marzo
Grupo de José María Valpuesta (CNB.CSIC)

REFERENCIA DEL GRUPO E INVESTIGADOR
Inés Muñoz y Hugo Yébenes trabajan como investigadora y estudiante predoctoral en los grupos de Cristalografía de Macromoléculas del CNIO y el grupo de estructura y función de chaperonas moleculares del CNB-CSIC, respectivamente. El trabajo de ambos grupos se centra en el estudio de complejos macromoleculares mediante el uso de la cristalografía de rayos-X y la microscopía electrónica.

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