The chaperonin ring assembly GroEL provides kinetic assistance to protein folding in the cell by binding non-native protein in the hydrophobic central cavity of an open ring and subsequently, upon binding ATP and the co-chaperonin GroES to the same ring, releasing polypeptide into a now hydrophilic encapsulated cavity where productive folding occurs in isolation. The fate of polypeptide during binding, encapsulation, and folding in the chamber has been the subject of recent experimental studies and is reviewed and considered here. We conclude that GroEL, in general, behaves passively with respect to its substrate proteins during these steps. While binding appears to be able to rescue non-native polypeptides from kinetic traps, such rescue is most likely exerted at the level of maximizing hydrophobic contact, effecting alteration of the topology of weakly structured states. Encapsulation does not appear to involve ‘forced unfolding’, and if anything, polypeptide topology is compacted during this step. Finally, chamber-mediated folding appears to resemble folding in solution, except that major kinetic complications of multimolecular association are prevented.

In the mid-1950s, RNA was a somewhat mysterious molecule with unknown three-dimensional structure and little hard evidence of biological function. Changes began with the 1956 discoveries of the RNA double helix and the phenomenon of nucleic acid hybridization. Discovery of the DNA–RNA hybrid helix in 1960 opened the door to understanding biological information transfer. Single-crystal X-ray diffraction analysis made it possible to precisely define the RNA double helix, discover the novel L-shaped fold of transfer RNA (tRNA), and finally reveal the complete three-dimensional tRNA structure by 1974. By then, a functional understanding of protein synthesis had developed with an appreciation of the various roles of different RNA species. This was the era of RNA awakening.