CHAPERONINS

The molecular chaperones are a diverse set of protein families require d for the correct folding, transport and degradation of other proteins in vivo. There has been great progress in under standing the structur e and mechanism of action of the chaperonin family, exemplified by Esc herichia coli GroEL. The chaperonins are large, double-ring oligomeric proteins that act as containers for the folding of other protein subu nits. Together with its co-protein GroES, GroEL binds non-native polyp eptides and facilitates their refolding in an ATP-dependent manner. Th e action of the ATPase cycle causes the substrate-binding surface of G roEL to alternate in character between hydrophobic (binding/unfolding) and hydrophilic (release/folding). ATP binding initiates a series of dramatic conformational changes that bury the substrate-binding sites, lowering the affinity for non-native polypeptide. In the presence of ATP, GroES binds to GroEL, forming a large chamber that encapsulates s ubstrate proteins for folding. For proteins whose folding is absolutel y dependent on the full GroE system, ATP binding (but not hydrolysis) in the encapsulating ring is needed to initiate protein folding. Simil arly, ATP binding, but not hydrolysis, in the opposite GroEL ring is n eeded to release GroES, thus opening the chamber. If the released subs trate protein is still not correctly folded, it will go through anothe r round of interaction with GroEL.