InterPro domain: IPR033162

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 [ 1 ].

This entry represents tubulin-folding cofactor D (TBCD) and its homologues. Its ability to interact with beta tubulin is regulated via its interaction with ARL2 (ADP ribosylation factor-like protein 2), a small monomeric G protein. ARL2 inhibits the beta-tubulin GTPase activating protein (GAP) activity of TBCD, and its interaction with native tubulin dimers [ 2 , 3 ].

1. Tubulin-specific chaperones: components of a molecular machine that assembles the α/β heterodimer. Methods Cell Biol. 115, 155-71
2. ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of tubulin-folding cofactor D with native tubulin. J. Cell Biol. 149, 1087-96
3. Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics. Elife 4