GroEL/GroES‐mediated protein folding

The GroEL/GroES chaperonin system mediates essential kinetic assistance to protein folding by capturing non‐native species in an open ring of GroEL via hydrophobic contacts, preventing aggregation, and then carrying out folding in an encapsulated ring following binding of ATP/GroES. We have been studying the action of cooperative ATP binding within a ring, which mediates initial apical domain movements that both favor substrate protein binding and enable the initial association of GroES. Using an ATP hydrolysis‐defective version of GroEL, short‐time freezing, and cryoEM, the conformational trajectory of the apical domains has been studied. These observations have implications for the movements that follow initial GroES binding, which form the domed folding‐active ring. We have also continued to investigate the nature of folding in the GroES‐encapsulated GroEL ring, assessing active vs. passive behavior, using a number of approaches.