Mutational analysis of the Q i -site proton pathway in yeast cytochrome bc 1 complex.

The respiratory cytochrome bc ₁ complex functions as a protonmotive ubiquinol:cytochrome c oxidoreductase. Lysine 228 (K228) located within the quinol reduction (Q _i ) site of the bc ₁ complex, has been reported as a key residue for proton transfer during the redox chemistry cycle to substrate quinone at Q _i . In yeast, while single mutations had no effect, the combination of K228L and F225L resulted in a severe respiratory growth defect and inhibition of O ₂ consumption in intact cells. The inhibition was overcome by uncoupling the mitochondrial membrane or by suppressor mutations in the region of K228L-F225L. We propose that the K228L mutation introduces energetic (and kinetic) barriers into normal electron- and proton transfer chemistry at Q _i , which are relieved by dissipation of the opposing protonmotive force or through the restoration of favourable intraprotein proton transfer networks via suppressor mutation.
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