CHARACTERIZATION OF A FUNCTIONALLY IMPORTANT MOBILE DOMAIN OF GROES

ALTHOUGH genetic1 and biochemical2,3 evidence has established that Gro ES is required for the full function of the molecular chaperone, GroEL , little is known about the molecular details of their interaction. Gr oES enhances the cooperativity of ATP binding and hydrolysis by GroEL (refs 4, 5) and is necessary for release and folding of several GroEL substrates6. Here we report that native GroES has a highly mobile and accessible polypeptide loop whose mobility and accessibility are lost upon formation of the GroES/GroEL complex. In addition, lesions presen t in eight independently isolated mutant groES alleles map in the mobi le loop. Studies with synthetic peptides suggest that the loop binds i n a hairpin conformation at a site on GroEL that is distinct from the substrate-binding site. Flexibility may be required in the mobile loop s on the GroES seven-mer to allow them to bind simultaneously to sites on seven GroEL subunits, which may themselves be able to adopt differ ent arrangements, and thus to modulate allosterically GroEL/substrate affinity.