GroEL/GroES: Structure and function of a two-stroke folding machine

Recent structural and functional studies have greatly advanced our understa nding of the mechanism by which chaperonins (Cpn60) mediate protein folding , the final step in the accurate expression of genetic information. Escheri chia coli GroEL has a symmetric double-toroid architecture, which binds non native polypeptide substrates on the hydrophobic walls of its central cavit y. The asymmetric binding of ATP and cochaperonin GroES to GroEL triggers a major conformational change in the cis ring, creating an enlarged chamber into which the bound nonnative polypeptide is released. The structural chan ges that create the cis assembly also change the lining of the cavity wall from hydrophobic to hydrophilic, conducive to folding into the native state . ATP hydrolysis in the cis ring weakens it and primes the release of produ cts. When ATP and GroES bind to the trans ring, it forms a stronger assembl y, which disassembles the cis complex through negative cooperativity betwee n rings. The opposing function of the two rings operates as if the system h ad two cylinders, one expelling the products of the reaction as the other l oads up the reactants. One cycle of the reaction gives the polypeptide abou t 15 s to fold at the cost of seven ATP molecules. For some proteins, sever al cycles of GroEL assistance may be needed in order to achieve their nativ e states. (C) 1998 Academic Press.