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Abstract

The bacterial chaperonin GroEL and its cofactor GroES constitute the paradigmatic molecular machine of protein folding. GroEL is a large double-ring cylinder with ATPase activity that binds non-native substrate protein (SP) via hydrophobic residues exposed towards the ring center. Binding of the lid-shaped GroES to GroEL displaces the bound protein into an enlarged chamber, allowing folding to occur unimpaired by aggregation. GroES and SP undergo cycles of binding and release, regulated allosterically by the GroEL ATPase. Recent structural and functional studies are providing insights into how the physical environment of the chaperonin cage actively promotes protein folding, in addition to preventing aggregation. Here, we review different models of chaperonin action and discuss issues of current debate.