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.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio al mejor artículo de jóvenes de la SEBBM, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

01-02-2019

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Leer más

Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons

02-01-2019

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of...

Leer más

Dynamic acetylation of cytosolic phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions

01-12-2018

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts...

Leer más

The Helicase PIF1 Facilitates Resection overSequences Prone to Forming G4 Structures

02-11-2018

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). The decision between these two routes of DNA repair is...

Leer más

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

01-10-2018

The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may...

Leer más

Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

03-09-2018

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear...

Leer más

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

01-08-2018

The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of...

Leer más

A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets

02-07-2018

Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering...

Leer más

Deciphering the Dynamic Transcriptional and Post-transcriptional Networks of Macrophages in the Healthy Heart and after Myocardial Injury

01-06-2018

Our group is interested in the behavior and transcriptional regulation of macrophages in the context of complex disease environments. We have generated a whole transcriptome dataset (mRNA, miRNA, and lincRNA)...

Leer más

Synaptic activity‐induced glycolysis facilitates membrane lipid provision and neurite outgrowth

01-05-2018

La formación de nuevas neuritas es un proceso clave para el correcto desarrollo del sistema nervioso. El crecimiento neurítico requiere la generación de nuevas membranas. No obstante, los cambios metabólicos...

Leer más

Socios Protectores