InterPro domain: IPR004226

This entry represents tubulin binding cofactor A (TBCA) from animal, plants and fungi. Human TBCA functions as a molecular chaperone for beta-tubulin [ 1 ]. Budding yeast TBCA, also known as Rbl2, may bind transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic [ 2 ]. The sequence identity of Rbl2 and human TBCA is only 32%, they appear to be structurally distinct and may interact with beta-tubulin by different mechanisms [ 3 ].

The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP [ 4 ].

1. Three-dimensional structure of human tubulin chaperone cofactor A. J. Mol. Biol. 318, 1139-49
2. Protection from free beta-tubulin by the beta-tubulin binding protein Rbl2p. Mol. Cell. Biol. 22, 138-47
3. Model for the yeast cofactor A-beta-tubulin complex based on computational docking and mutagensis. J. Mol. Biol. 341, 1343-54
4. Tubulin-specific chaperones: components of a molecular machine that assembles the α/β heterodimer. Methods Cell Biol. 115, 155-71