The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex

Antony R. Crofts, Sangjin Hong, Charles Wilson, Rodney Burton, Doreen Victoria, Chris Harrison, Klaus Schulten

Research output: Contribution to journalReview article

Abstract

1. Recent results suggest that the major flux is carried by a monomeric function, not by an intermonomer electron flow. 2. The bifurcated reaction at the Qo-site involves sequential partial processes, - a rate limiting first electron transfer generating a semiquinone (SQ) intermediate, and a rapid second electron transfer in which the SQ is oxidized by the low potential chain. 3. The rate constant for the first step in a strongly endergonic, proton-first-then-electron mechanism, is given by a Marcus-Brønsted treatment in which a rapid electron transfer is convoluted with a weak occupancy of the proton configuration needed for electron transfer. 4. A rapid second electron transfer pulls the overall reaction over. Mutation of Glu-295 of cyt b shows it to be a key player. 5. In more crippled mutants, electron transfer is severely inhibited and the bell-shaped pH dependence of wildtype is replaced by a dependence on a single pK at ~ 8.5 favoring electron transfer. Loss of a pK ~ 6.5 is explained by a change in the rate limiting step from the first to the second electron transfer; the pK ~ 8.5 may reflect dissociation of QH. 6. A rate constant (< 103 s- 1) for oxidation of SQ in the distal domain by heme bL has been determined, which precludes mechanisms for normal flux in which SQ is constrained there. 7. Glu-295 catalyzes proton exit through H+ transfer from QH, and rotational displacement to deliver the H+ to exit channel(s). This opens a volume into which Q- can move closer to the heme to speed electron transfer. 8. A kinetic model accounts well for the observations, but leaves open the question of gating mechanisms. For the first step we suggest a molecular "escapement"; for the second a molecular ballet choreographed through coulombic interactions. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.

Original languageEnglish (US)
Pages (from-to)1362-1377
Number of pages16
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1827
Issue number11-12
DOIs
StatePublished - 2013

Keywords

  • Bifurcated reaction of Q-cycle
  • Control and gating
  • H exit pathway
  • Kinetic model
  • Semiquinone occupancy

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

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    Crofts, A. R., Hong, S., Wilson, C., Burton, R., Victoria, D., Harrison, C., & Schulten, K. (2013). The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex. Biochimica et Biophysica Acta - Bioenergetics, 1827(11-12), 1362-1377. https://doi.org/10.1016/j.bbabio.2013.01.009