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The structure of the complex between a-tubulin, TBCE and TBCB reveals a tubulin dimer dissociation mechanism

Abstract: Tubulin proteostasis is regulated by a group of molecular chaperones termed tubulin cofactors (TBC). Whereas tubulin heterodimer formation is well-characterized biochemically, its dissociation pathway is not clearly understood. Here, we carried out biochemical assays to dissect the role of the human TBCE and TBCB chaperones in a-tubulin–b-tubulin dissociation. We used electron microscopy and image processing to determine the three-dimensional structure of the human TBCE, TBCB and a-tubulin (aEB) complex, which is formed upon a-tubulin–b-tubulin heterodimer dissociation by the two chaperones. Docking the atomic structures of domains of these proteins, including the TBCE UBL domain, as we determined by X-ray crystallography, allowed description of the molecular architecture of the aEB complex. We found that heterodimer dissociation is an energy-independent process that takes place through a disruption of the a-tubulin–b-tubulin interface that is caused by a steric interaction between b-tubulin and the TBCE cytoskeleton-associated protein glycine-rich (CAP-Gly) and leucine-rich repeat (LRR) domains. The protruding arrangement of chaperone ubiquitin-like (UBL) domains in the aEB complex suggests that there is a direct interaction of this complex with the proteasome, thus mediating a-tubulin degradation.

 Autoría: Serna M., Carranza G., Martín-Benito J., Janowski R., Canals A., Coll M., Zabala J.C., Valpuesta J.M.,

 Fuente: Journal of Cell Science, 2015, 128(9), 1824-1834

 Editorial: Company of Biologists

 Fecha de publicación: 01/05/2015

 Nº de páginas: 17

 Tipo de publicación: Artículo de Revista

 DOI: 10.1242/jcs.167387

 ISSN: 0021-9533,1477-9137

 Url de la publicación: http://jcs.biologists.org/content/128/9/1824

Autoría

MARINA, SERNA

GERARDO CARRANZA FERRER

JAIME MARTIN BENITO

JANOWSKI, ROBERT

CANALS, ALBERT

COLL, MIQUEL

JUAN CARLOS ZABALA OTAÑO

JOSE MARIA VALPUESTA MORALEJO