Co-translational formation of disulfides guides folding of the SARS-CoV-2 receptor binding domain.

ABSTRACT: Many secreted proteins, including viral proteins, contain multiple disulfide bonds. How disulfide formation is coupled to protein folding in the cell remains poorly understood at the molecular level. Here, we combine experiment and simulation to address this question as it pertains to the SARS-CoV-2 receptor binding domain (RBD). We show that the RBD can only refold reversibly if its native disulfides are present before folding. But in their absence, the RBD spontaneously misfolds into a nonnative, molten-globule-like state that is structurally incompatible with complete disulfide formation and that is highly prone to aggregation. Thus, the RBD native structure represents a metastable state on the protein's energy landscape with reduced disulfides, indicating that nonequilibrium mechanisms

SUBMITTER: Bitran A 

PROVIDER: S-EPMC10465708 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature