Identification of an on-pathway intermediate illuminates the kinetic competition between protein folding and misfolding.

ABSTRACT: Our current understanding of protein folding is based predominantly on studies of small (<150 aa) proteins that refold reversibly from a chemically denatured state. However, as protein length increases so does the competition between off-pathway misfolding and on-pathway folding, creating a more complex energy landscape ("folding funnel"). Little is known about how intermediates populated during the folding of larger proteins affect navigation of this more complex landscape. Previously, we reported extremely slow folding rates for the 539 aa β-helical passenger domain of pertactin (P.69T), including conditions that favor the formation of a kinetically trapped, off-pathway partially folded state (PFS). Existence of an on-pathway intermediate for P.69T folding was speculated but its characte

SUBMITTER: Luan Q 

PROVIDER: S-EPMC12337298 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature