The bacterial chaperonin GroEL and its cochaperone GroES belong to the Hsp60/Hsp10 (aka Cpn60/Cpn10) family of heat shock proteins. Bacterial GroEL is an ≈ 800-kDa hollow cylinder consisting of two seven-subunit rings stacked back to back. GroEL uses a set of hydrophobic residues located at either end of the cylinder to capture non-native substrate and to interact with its co-chaperone GroES, a 70-kDa, dome-shaped homoheptamer. In vivo, binding of client proteins occurs on the ring of GroEL that is not complexed to GroES (known as the trans ring) and involves multiple contacts with the substrate that lead to nanomolar dissociation constants. GroEL can fold proteins up to 60-kDa in size and appears to exhibit a preference for compact intermediates consisting of two or more domains with alpha/beta-folds that are enriched in hydrophobic and basic residues.

GroEL-mediated protein folding is believed to involve the following sequence of events: (1) substrate binding to the nucleotide-free trans ring; (2) binding of 7 ATP molecules and encapsulation by GroES which results in substrate release in an enlarged and now hydrophilic cavity as well as ejection of bound ADP and GroES from the opposite ring; (3) substrate folding timed by the hydrolysis of ATP (≈ 10s); and (4) release of GroES, ADP and either properly folded protein or folding intermediate caused by the binding of 7 ATPs and fresh substrate to the opposite ring. If the ejected substrate still exhibits significant surface hydrophobicity, it will be re-captured by GroEL and the above cycle repeated until a correct conformation is reached.

More information on the GroEL-GroES system is available on Helen Saibil's site.