CCTalpha

CCT-α (also known as TCP-1) is a member of the class of group II chaperonins that are present in the cytosol of eukaryotes. In vivo most of the newly synthesized polypeptides acquire their three-dimensional structure with the assistance of molecular chaperones that maximize productive folding. Each CCT subunit consists of three domains: an equatorial domain containing an ATP-binding site, an apical domain responsible for target protein interaction, and the intermediate domain connecting the other two. The apical domain contains a helical protrusion, which is involved in opening and closing the central cavity of the chaperonin. The whole CCT complex mediates the folding driven by ATP binding, and hydrolysis has a crucial function in vivo in the folding of newly translated tubulins (α, β and γ) and actin, which are its major target proteins. Actin and tubulins are delivered to the CCT complex by prefoldin (also referred to as Gim C) by means of direct interactions. Although the interaction with prefoldin is not essential for efficient substrate binding to CCT, the loss of Gim C function in yeast results in a substantially reduced efficiency of actin and tubulin folding. The assembly of some protein oligomeric complexes may be dependent on the CCT function. In fact, for some CCT target proteins, such as cyclin E and VHL, their release from the chaperonin and completion of folding are coupled to their assembly into an oligomeric complex. After interacting with CCT, tubulins follow two different folding pathways: α-tubulin is captured by cofactor B, and β-tubulin by cofactor A. Then cofactors E and D capture α-tubulin and β-tubulin, respectively. The two pathways converge and α-tubulin, β-tubulin, cofactor E and cofactor D form a super-complex. Cofactor C interacts with this complex and on hydrolysis of GTP the assembled competent α/β-tubulin heterodimers are released.