The family of molecular chaperones termed chaperonins can be categorised based on their sequences as either group I or group II chaperonins. The first includes the eubacterial chaperone GroEL and chaperonins from mitochondria and chloroplasts; the second includes the archaeal chaperonins and CCT, which is found in the cytoplasm of all eukaryotic cells and is essential in yeast (Stoldt et al 1996
). All chaperonins are large, barrel-shaped oligomers consisting of two rings of subunits stacked back-to-back surrounding a central cavity. In the case of the eubacterial chaperonin GroEL, the term ‘Anfinsen Cage’ has been adopted (Ellis 1996
) to describe the protective environment provided by this central cavity in which proteins can proceed to their native state.
GroEL and the archaebacterial chaperonins are formed from one and three subunit species, respectively, whilst CCT consists of eight distinct subunits, which are the products of individual genes. The eight CCT subunits, named α, β, γ, δ,
, ζ, η and θ (Cct1 to 8 in yeast), each occupy a fixed position in the chaperonin ring (Liou and Willison 1997
) as shown in Fig. . Each consists of an equatorial domain that contains the ATP-binding site and both inter- and intra-ring contact sites, an apical, substrate-binding domain and an intermediate linker domain that relays nucleotide-induced conformational changes from the equatorial to the apical domains. These subunits display the most divergence in sequence in their apical, substrate-binding domains. Unlike GroEL, which is assisted by the lid-forming co-chaperone GroES, CCT has no such co-chaperone. Instead, a built-in lid is formed from helical protrusions that erupt from the apical domains of all eight CCT subunits and facilitate the encapsulation of folding substrates within the chaperonin cavity. The phasing of the two chaperonin rings has recently been solved using antibody labelling followed by cryoelectron single-particle microscopy and three-dimensional reconstructions (Martin-Benito et al 2007
) as shown in Fig. . The proposed hierarchy amongst CCT subunits in their binding of ATP, as judged by mutational analysis in yeast (Lin and Sherman 1997
) and by electron microscopy (Rivenzon-Segal et al 2005
), is in good agreement with the overall structure of CCT. Therefore, the subunits thought to initiate ATP binding in one ring are in close proximity to those subunits at the end of this cascade in the other ring (Fig. ).
Fig. 1 Subunit arrangement and three-dimensional analysis of CCT. (A) Cartoon diagram to illustrate the positioning of the eight CCT subunits within the chaperonin ring according to (Liou and Willison 1997). (B) Cryoelectron single-particle reconstruction of (more ...)