GroEL‐Mediated protein folding

I Architecture of GroEL and GroES and the reaction pathwayA. Architecture of the chaperonins B. Reaction pathway of GroEL‐GroES‐mediated foldingII. Polypeptide bindingA. A parallel network of chaperones binding polypeptides in vivo B. Polypeptide binding in vitro1. Role of hydrophobicity in recognition 2. Homologous proteins with differing recognition—differences in primary structure versus effects on folding pathway 3. Conformations recognized by GroELa. Refolding studies b. Binding of metastable intermediates c. Conformations while stably bound at GroEL4. Binding constants and rates of association 5. Conformational changes in the substrate protein associated with binding by GroELa. Observations b. Kinetic versus thermodynamic action of GroEL in mediating unfolding c. Crossing the energy landscape in the presence of GroELIII. ATP binding and hydrolysis—driving the reaction cycleIV. GroEL‐GroES‐polypeptide ternary complexes—the folding‐active cis complexA. Cis and trans ternary complexes B. Symmetric complexes C. The folding‐active intermediate of a chaperonin reaction—cis ternary complex D. The role of the cis space in the folding reaction E. Folding governed by a “timer” mechanism F. Release of nonnative polypeptides during the GroEL‐GroES reaction G. Release of both native and nonnative forms under physiologic conditions H. A role for ATP binding, as well as hydrolysis, in the folding cycleV. Concluding remarks