The GroEL–GroES Chaperonin Machine: A Nano-Cage for Protein Folding

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.

TrendsThe group I chaperonin GroEL and its cofactor GroES are essential components of the cellular machinery of protein folding in bacteria. Homologous chaperonins occur in mitochondria and chloroplast, while more distantly related group II chaperonins are found in archaea and the eukaryotic cytosol.GroEL is a double-ring complex with ATPase activity that binds non-native SP in the ring opening. Binding of the lid-shaped GroES to GroEL results in the displacement of SP into an enclosed nano-cage for folding to occur unimpaired by aggregation.GroEL, non-native protein, and GroES undergo ATP-regulated binding and release cycles.Recent advances indicate that the physical environment of the GroEL–GroES cage can accelerate the folding of some SPs. An effect of steric confinement of SP in the cage may contribute to the rate enhancement of folding.