Function and regulation of cytosolic molecular chaperone CCT.

Molecular chaperones are a group of proteins that assists in the folding of newly synthesized proteins or in the refolding of denatured proteins. The cytosolic chaperonin-containing t-complex polypeptide 1 (CCT) is a molecular chaperone that plays an important role in the folding of proteins in the eukaryotic cytosol. Actin, tubulin, and several other proteins are known to be folded by CCT, and an estimated 15% of newly translated proteins in mammalian cells are folded with the assistance of CCT. CCT differs from other chaperonin family proteins in its subunit composition, which consists of eight subunit species comprising the CCT 16-mer double-ring-like complex. CCT preferentially recognizes quasinative (or partially folded) intermediates, whereas its Escherichia coli homologue GroEL recognizes more unfolded intermediates, especially those displaying hydrophobic surfaces. Molecular evolutionary analyses have suggested that each subunit species has a specific function in addition to contributing to a common ATPase activity. Consistent with this view, it has been suggested that each subunit recognizes specific substrate proteins (or their parts) and that they collectively modulate the ATPase activity of the complex. The overall expression of CCT in mammalian cells is primarily dependent on cell growth, but each subunit exhibits an individual patterns of expression. Recent progress in CCT research is reviewed, focusing particularly on CCT function and expression. From these observations, the possible roles of the distinct subunits in CCT-assisted folding in the eukaryotic cytosol are discussed.