Mechanism of substrate recognition by the chaperonin GroEL

The bacterial chaperonin GroEL functions with its cofactor GroES in assisting the folding of a wide range of proteins in an ATP-dependent manner. GroEL-GroES constitute one of the main chaperone systems in the Escherichia coli cytoplasm. The chaperonin facilitates protein folding by enclosing substrate proteins in a cage defined by the GroEL cylinder and the GroES cap where folding can take place in a protected environment. The in vivo role of GroEL has recently been elucidated. GroEL is found to interact with 10-15% of newly synthesized proteins, with a strong preference for proteins in the molecular weight range of 20-60 kDa. A large number of GroEL substrates have been identified and were found to preferentially contain proteins with multiple alphabeta, domains that have alpha-helices and beta-sheets with extensive hydrophobic surfaces. Based on the preferential binding of GroEL to these proteins and structural and biochemical data, a model of substrate recognition by GroEL is proposed. According to this model, binding takes place preferentially between the hydrophobic residues in the apical domains of GroEL and the hydrophobic faces exposed by the beta-sheets or alpha-helices in the alphabeta domains of protein substrates.