The mitochondrial intermembrane space oxireductase mia40 funnels the oxidative folding pathway of the cytochrome c oxidase assembly protein cox19

Hugo Fraga, Joan Josep Bech-Serra, Francesc Canals, Gabriel Ortega, Oscar Millet, Salvador Ventura

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Mia40-catalyzed disulfide formation drives the import of many proteins into the mitochondria. Here we characterize the oxidative folding of Cox19, a twin CX9C Mia40 substrate. Cox19 oxidation is extremely slow, explaining the persistence of import-competent reduced species in the cytosol. Mia40 accelerates Cox19 folding through the specific recognition of the third Cys in the second helical CX9C motif and the subsequent oxidation of the inner disulfide bond. This renders a native-like intermediate that oxidizes in a slow uncatalyzed reaction into native Cox19. The same intermediate dominates the pathway in the absence of Mia40, and chemical induction of an α-helical structure by trifluoroethanol suffices to accelerate productive folding and mimic the Mia40 folding template mechanism. The Mia40 role is to funnel a rough folding landscape, skipping the accumulation of kinetic traps, providing a rationale for the promiscuity of Mia40. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)9852-9864
JournalJournal of Biological Chemistry
Volume289
Issue number14
DOIs
Publication statusPublished - 4 Apr 2014

Fingerprint Dive into the research topics of 'The mitochondrial intermembrane space oxireductase mia40 funnels the oxidative folding pathway of the cytochrome c oxidase assembly protein cox19'. Together they form a unique fingerprint.

  • Cite this