The crystal structure of a GroEL/peptide complex: Plasticity as a basis for substrate diversity

The chaperonin GroEL is a double toriodal assembly that with its cochaperon in GroES facilitates protein folding with an ATP-dependent mechanism. Nonna tive conformations of diverse protein substrates bind to the apical domains surrounding the opening of the double toroid's central cavity. Using phage display, we have selected peptides with high affinity for the isolated api cal domain. We have determined the crystal structures of the complexes form ed by the most strongly bound peptide with the isolated apical domain, and with GroEL. The peptide interacts with the groove between paired or helices in a manner similar to that of the GroES mobile loop. Our structural analy sis, combined with other results, suggests that various modes of molecular plasticity are responsible for tight promiscuous binding of nonnative subst rates and their release into the shielded cis assembly.