Structural highlights
FunctionNU1M_YARLI Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Publication Abstract from PubMedComplex I (proton-pumping NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain and a significant source of reactive oxygen species (ROS). We hypothesized that during energy conversion by complex I, electron transfer onto ubiquinone triggers the concerted rearrangement of three protein loops of subunits ND1, ND3, and 49-kDa thereby generating the power-stoke driving proton pumping. Here we show that fixing loop TMH1-2(ND3) to the nearby subunit PSST via a disulfide bridge introduced by site-directed mutagenesis reversibly disengages proton pumping without impairing ubiquinone reduction, inhibitor binding or the Active/Deactive transition. The X-ray structure of mutant complex I indicates that the disulfide bridge immobilizes but does not displace the tip of loop TMH1-2(ND3). We conclude that movement of loop TMH1-2(ND3) located at the ubiquinone-binding pocket is required to drive proton pumping corroborating one of the central predictions of our model for the mechanism of energy conversion by complex I proposed earlier. Locking loop movement in the ubiquinone pocket of complex I disengages the proton pumps.,Cabrera-Orefice A, Yoga EG, Wirth C, Siegmund K, Zwicker K, Guerrero-Castillo S, Zickermann V, Hunte C, Brandt U Nat Commun. 2018 Oct 29;9(1):4500. doi: 10.1038/s41467-018-06955-y. PMID:30374105[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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