The cytochrome c folding landscape revealed by electron-transfer kinetics

Jennifer C. Lee, I-Jy Chang, Harry B. Gray, Jay R. Winkler

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

We have investigated the folding energy landscape of cytochrome c by exploiting the widely different electron-transfer (ET) reactivities of buried and exposed Zn(II)-substituted hemes. An electronically excited Zn-porphyrin in guanidine hydrochloride denatured Zn-substituted cytochrome c (Zn-cyt c) reduces ruthenium(III) hexaammine about ten times faster than when embedded in the fully folded protein. Measurements of ET kinetics during Zn-cyt c folding reveal a burst intermediate in which one-third of the ensemble has a protected Zn-porphyrin and slow ET kinetics; the remaining fraction exhibits fast ET characteristic of a solvent-exposed redox cofactor. The ET data show that, under solvent conditions favoring the folded protein, collapsed non-native structures are not substantially more stable than extended conformations, and that the two populations interchange rapidly. Most of the folding free energy, then, is released when compact structures evolve into the native fold.

Original languageEnglish
Pages (from-to)159-164
Number of pages6
JournalJournal of Molecular Biology
Volume320
Issue number2
DOIs
Publication statusPublished - 2002 Jan 1

Fingerprint

Cytochromes c
Electrons
Porphyrins
Ruthenium
Guanidine
Heme
Oxidation-Reduction
Proteins
Population

Keywords

  • Burst intermediate
  • Cytochrome c
  • Electron transfer
  • Protein folding

ASJC Scopus subject areas

  • Molecular Biology

Cite this

The cytochrome c folding landscape revealed by electron-transfer kinetics. / Lee, Jennifer C.; Chang, I-Jy; Gray, Harry B.; Winkler, Jay R.

In: Journal of Molecular Biology, Vol. 320, No. 2, 01.01.2002, p. 159-164.

Research output: Contribution to journalArticle

Lee, Jennifer C. ; Chang, I-Jy ; Gray, Harry B. ; Winkler, Jay R. / The cytochrome c folding landscape revealed by electron-transfer kinetics. In: Journal of Molecular Biology. 2002 ; Vol. 320, No. 2. pp. 159-164.
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