Journal
JOURNAL OF CELL SCIENCE
Volume 128, Issue 9, Pages 1824-1834Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.167387
Keywords
Tubulin; Protein degradation; Chaperone; Folding cofactor; Microtubule; TBCE; TBCB
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Funding
- Spanish Ministry of Science and Innovation [CONSOLIDER CSD 2006-23, BFU2011-22588, BFU2011-25090, BFU2013-44202, BFU2010-18948]
- Madrid Regional Government [S2013/MIT-2807]
- Generalitat de Catalunya [SGR2009-1309]
- Instituto de Investigacion Marques de Valdecilla (IDIVAL)
- Universidad de Cantabria [02.VP01.64005]
- European Commission [260644]
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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 alpha-tubulin-beta-tubulin dissociation. We used electron microscopy and image processing to determine the three-dimensional structure of the human TBCE, TBCB and alpha-tubulin (alpha EB) complex, which is formed upon alpha-tubulin-beta-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 alpha EB complex. We found that heterodimer dissociation is an energy-independent process that takes place through a disruption of the alpha-tubulin-beta-tubulin interface that is caused by a steric interaction between beta-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 alpha EB complex suggests that there is a direct interaction of this complex with the proteasome, thus mediating alpha-tubulin degradation.
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