Mechanism of substrate recognition by the chaperonin GroEL

The bacterial chaperonin GroEL functions with its cofactor GroES in assisti ng the folding of a wide range of proteins in an ATP-dependent manner. GroE L-GroES constitute one of the main chaperone systems in the Escherichia col i cytoplasm. The chaperonin facilitates protein folding by enclosing substr ate proteins in a cage defined by the GroEL cylinder and the GroES cap wher e folding can take place in a protected environment. The in vivo role of Gr oEL has recently been elucidated. GroEL is found to interact with 10-15% of newly synthesized proteins, with a strong preference for proteins in the m olecular weight range of 20-60 kDa. A large number of GroEL substrates have been identified and were found to preferentially contain proteins with mul tiple alpha beta domains that have alpha -helices and beta -sheets with ext ensive hydrophobic surfaces. Based on the preferential binding of GroEL to these proteins and structural and biochemical data, a model of substrate re cognition by GroEL is proposed. According to this model, binding takes plac e preferentially between the hydrophobic residues in the apical domains of GroEL and the hydrophobic faces exposed by the beta -sheets or alpha -helic es in the alpha beta domains of protein substrates.