CCT/TRiC chaperonin-mediated folding

The chaperonin containing TCP-1 (CCT, also called TRiC) is the group II chaperonin of the eukaryotic cytosol. It is a double ring of two hetero-octameric rings, each made of one copy of eight paralogous subunits (CCT1/alpha to CCT8/theta), and this subunit set is conserved from yeast to nematodes and mammals. Each subunit has an equatorial ATP-binding domain, an intermediate hinge and an apical client-binding domain with a built-in lid, so CCT closes its folding chamber without a separate co-chaperonin. Cycles of ATP binding and hydrolysis drive lid closure and folding of clients held in the chamber. Nucleotide use is asymmetric: only four subunits (CCT1, CCT2, CCT4 and CCT5) bind ATP at physiological concentrations, and ATP binding by the other four is dispensable in vivo. The main obligate clients are actin and tubulin. Nascent actin and tubulin chains are captured by prefoldin (GimC in budding yeast), a jellyfish-shaped heterohexamer of two alpha-class and four beta-class subunits that binds non-native chains without ATP, docks on CCT and hands them over, raising the rate and yield of folding. In yeast, loss of prefoldin or CCT impairs actin- and tubulin-based cytoskeletal functions. In C. elegans, CCT depletion disrupts actin and microtubule organization and causes intestinal microvillus loss, prefoldin loss lowers alpha-tubulin levels and slows microtubule growth, and raising the CCT8 subunit level in somatic tissues extends lifespan in a CCT-dependent way.

Boundary. This module covers cytosolic group II chaperonin folding in eukaryotes: client delivery by prefoldin, then ATP-driven folding in the CCT chamber. The context taxon is Eukaryota because the eight-subunit CCT and the six-subunit prefoldin are present, as orthologous subunit sets, in fungi, animals and other eukaryotes, and the representative members span budding yeast, C. elegans and human. Archaea have prefoldin and group II chaperonins (thermosomes) of simpler composition; they are outside this module. No variant_sets are used: subunit composition, ring order and the prefoldin hand-off are conserved across the represented lineages, and no lineage replaces a role with an unrelated protein. Activity placement. Folding activity belongs to the assembled hetero-oligomer, so the complex-level MF GO:0140662 (ATP-dependent protein folding chaperone) is placed on the CCT complex annoton, and individual subunits are active units. Each subunit role is an ortholog group (FAMILY selector) represented by the worm, yeast and, where reviewed, human protein. All eight CCT subunits fall in the single PANTHER family PTHR11353 (CHAPERONIN), and its subunit subfamilies are split by lineage, so no PANTHER id is asserted for the individual CCT subunit groups. The prefoldin subunit groups each have their own PANTHER family, and those ids match the UniProt cross-references of every representative. Following PMID:23041314, ATP binding (GO:0005524) is given only on the four high-affinity subunits CCT1, CCT2, CCT4 and CCT5; CCT3, CCT6, CCT7 and CCT8 carry no subunit-level MF beyond contributing to GO:0140662. Gene reviews are not fully consistent on this point. The worm cct-8 review accepts ATP binding as a core function of CCT-8, although CCT8 is a low-affinity subunit. The yeast TCP1, CCT3, CCT5, CCT6 and CCT7 reviews give ATP hydrolysis activity (GO:0016887) as the subunit MF, the yeast CCT2 and CCT4 reviews give ATP binding, and the yeast CCT8 review gives only GO:0140662. The module follows the subunit ATP-affinity data and records these discrepancies here without changing the reviews. Prefoldin is an optional part. It is needed for efficient actin and tubulin biogenesis but not for all CCT clients, and CCT can fold clients that reach it without prefoldin. Its complex-level activity is given as the ATP-independent GO:0044183 protein folding chaperone, since GO:0051082 unfolded protein binding is obsolete. The C. elegans PFD-4 subunit is divergent and its loss reportedly gives no visible phenotype, so its contribution to worm prefoldin is uncertain; human PFDN4 is listed as the better-supported representative of that role. PFD-6/PFDN6 and other prefoldin subunits also occur in the prefoldin-like R2TP/PAQosome complex, which is outside this module. The C. elegans CCT-4 subunit has a reported nuclear role in assembling meiotic HORMAD proteins into chromosome axes (PMID:41136395); that nuclear function is also outside this module. Post-chaperonin tubulin folding cofactors (GO:0007023 post-chaperonin tubulin folding pathway), the HSP70/HSP90 systems and the mitochondrial group I chaperonin HSP60 are outside the boundary. HSP-60 co-purified with worm CCT in one study (PMID:9434769) but is a separate, mitochondrial machine. Clients (actins, alpha- and beta-tubulins and WD40 proteins) are substrates, not members. No production GO-CAM in gocams/index.tsv contains these proteins. Relation to MODULE:bacterial_groel_groes_chaperonin_folding. Both are ATP-driven cage chaperonins. GroEL is a homo-heptameric double ring capped by the separate GroES lid. CCT is a hetero-octameric double ring with a built-in lid and subunit-specific client-binding surfaces. The two are kept as separate modules, not variants of one, because the subunit composition, lid mechanism and client sets differ. A concrete D. melanogaster instance of the CCT complex, generated from the FlyBase CCT gene group, is MODULE:dmel_cct_chaperonin; it uses the same complex-level placement of GO:0140662.