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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.



Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: J Cell Sci. 2015 May 1;128(9):1824-34

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

Autores/as

MARINA, SERNA
GERARDO CARRANZA FERRER
JAIME MARTIN BENITO
JANOWSKI, ROBERT
CANALS, ALBERT
COLL, MIQUEL
JOSE MARIA VALPUESTA MORALEJO