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Publication Abstract from PubMed

Two independent structures of the proton-pumping, respiratory cytochrome bo(3) ubiquinol oxidase (cyt bo(3) ) have been determined by cryogenic electron microscopy (cryo-EM) in styrene-maleic acid (SMA) copolymer nanodiscs and in membrane scaffold protein (MSP) nanodiscs to 2.55- and 2.19-A resolution, respectively. The structures include the metal redox centers (heme b, heme o(3) , and Cu(B)), the redox-active cross-linked histidine-tyrosine cofactor, and the internal water molecules in the proton-conducting D channel. Each structure also contains one equivalent of ubiquinone-8 (UQ8) in the substrate binding site as well as several phospholipid molecules. The isoprene side chain of UQ8 is clamped within a hydrophobic groove in subunit I by transmembrane helix TM0, which is only present in quinol oxidases and not in the closely related cytochrome c oxidases. Both structures show carbonyl O1 of the UQ8 headgroup hydrogen bonded to D75(I) and R71(I) In both structures, residue H98(I) occupies two conformations. In conformation 1, H98(I) forms a hydrogen bond with carbonyl O4 of the UQ8 headgroup, but in conformation 2, the imidazole side chain of H98(I) has flipped to form a hydrogen bond with E14(I) at the N-terminal end of TM0. We propose that H98(I) dynamics facilitate proton transfer from ubiquinol to the periplasmic aqueous phase during oxidation of the substrate. Computational studies show that TM0 creates a channel, allowing access of water to the ubiquinol headgroup and to H98(I).

Cryo-EM structures of Escherichia coli cytochrome bo(3) reveal bound phospholipids and ubiquinone-8 in a dynamic substrate binding site.,Li J, Han L, Vallese F, Ding Z, Choi SK, Hong S, Luo Y, Liu B, Chan CK, Tajkhorshid E, Zhu J, Clarke O, Zhang K, Gennis R Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):e2106750118. doi: , 10.1073/pnas.2106750118. PMID:34417297^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.