Dual Action of ATP Hydrolysis Couples Lid Closure to Substrate Release into the Group II Chaperonin Chamber

SummaryGroup II chaperonins are ATP-dependent ring-shaped complexes that bind nonnative polypeptides and facilitate protein folding in archaea and eukaryotes. A built-in lid encapsulates substrate proteins within the central chaperonin chamber. Here, we describe the fate of the substrate during the nucleotide cycle of group II chaperonins. The chaperonin substrate-binding sites are exposed, and the lid is open in both the ATP-free and ATP-bound prehydrolysis states. ATP hydrolysis has a dual function in the folding cycle, triggering both lid closure and substrate release into the central chamber. Notably, substrate release can occur in the absence of a lid, and lid closure can occur without substrate release. However, productive folding requires both events, so that the polypeptide is released into the confined space of the closed chamber where it folds. Our results show that ATP hydrolysis coordinates the structural and functional determinants that trigger productive folding.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (236 K)Download as PowerPoint slideHighlights► ATP hydrolysis has a dual function in the folding cycle of group II chaperonins ► ATP hydrolysis triggers substrate release by creating a new lateral subunit interface ► Closing the built-in lid over the chaperonin chamber requires ATP hydrolysis ► Folding requires both events, so the polypeptide is released in the closed chamber