Abstract

Chaperones have been speculated to affect the protein conformational search for their native state. We address this issue by manipulating single protein chains using optical tweezers. We found that the chaperone Trigger Factor binds folded structures smaller than one domain, which are then stable for seconds and ultimately convert to the native state. Trigger Factor stimulates native folding by suppressing misfolding interactions between domains in constructs of repeated MBP domains. The results indicate that Trigger Factor promotes correct folding by protecting partially folded states from interactions that produce stable misfolded states. As Trigger Factor interacts with most newly-synthesized proteins in Escherichia coli, these findings may be of general importance in understanding protein folding pathways.