TCB Publications - Abstract

Antony R. Crofts, Sangjin Hong, Charles Wilson, Rodney Burton, Doreen Victoria, Chris Harrison, and Klaus Schulten. The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex. Biochimica et Biophysica Acta, 1827:1362-1377, 2013. (PMC: PMC3995752)

CROF2013 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 Q$_{o}$-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 end-ergonic, proton-first-then-electron mechanism, is given by a Marcus–Br 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 $\sim$8.5 favoring electron transfer. Loss of a pK $\sim$6.5 is explained by a change in the rate limiting step from the first to the second electron transfer; the pK $\sim$8.5 may reflect dissociation of QH$\bullet$. 6. A rate constant ($<10^{3}$s$^{1}$) for oxidation of SQ in the distal domain by heme $b_{L}$ 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$\bullet$, and rotational displacement to deliver the H$^{+}$ to exit channel(s). This opens a volume into which Q$\bullet$ - 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.

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