The Molecular Evolution of the Qo Motif

Quinol oxidation in the catalytic quinol oxidation site (Q(o) site) of cytochrome (cyt) bc(1) complexes is the key step of the Q cycle mechanism, which laid the ground for Mitchell's chemiosmotic theory of energy conversion. Bifurcated electron transfer upon quinol oxidation enables proton uptake and release on opposite membrane sides, thus generating a proton gradient that fuels ATP synthesis in cellular respiration and photosynthesis. The Q(o) site architecture formed by cyt b and Rieske iron-sulfur protein (ISP) impedes harmful bypass reactions. Catalytic importance is assigned to four residues of cyt b formerly described as PEWY motif in the context of mitochondrial complexes, which we now denominate Q(o) motif as comprehensive evolutionary sequence analysis of cyt b shows substantial natural variance of the motif with phylogenetically specific patterns. In particular, the Q(o) motif is identified as PEWY in mitochondria, alpha- and epsilon-Proteobacteria, Aquificae, Chlorobi, Cyanobacteria, and chloroplasts. PDWY is present in Gram-positive bacteria, Deinococcus-Thermus and haloarchaea, and PVWY in beta- and gamma-Proteobacteria. PPWF only exists in Archaea. Distinct patterns for acidophilic organisms indicate environment-specific adaptations. Importantly, the presence of PDWY and PEWY is correlated with the redox potential of Rieske ISP and quinone species. We propose that during evolution from low to high potential electron-transfer systems in the emerging oxygenic atmosphere, cyt bc(1) complexes with PEWY as Q(o) motif prevailed to efficiently use high potential ubiquinone as substrate, whereas cyt b with PDWY operate best with low potential Rieske ISP and menaquinone, with the latter being the likely composition of the ancestral cyt bc(1) complex.