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Publication Abstract from PubMed

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 (alphaEB) 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 alphaEB 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 alphaEB complex suggests that there is a direct interaction of this complex with the proteasome, thus mediating alpha-tubulin degradation.

The structure of the complex between alpha-tubulin, TBCE and TBCB reveals a tubulin dimer dissociation mechanism.,Serna M, Carranza G, Martin-Benito J, Janowski R, Canals A, Coll M, Zabala JC, Valpuesta JM J Cell Sci. 2015 May 1;128(9):1824-34. doi: 10.1242/jcs.167387. Epub 2015 Apr 23. PMID:25908846^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.