Structural studies on aerobic and anaerobic respiratory complexes
Abstract: All respiratory pathways, whether aerobic or anaerobic, are based on formation of an electrochemical proton gradient called proton motive force (pmf) that drives ATP formation. Membrane-bound respiratory complexes translocate protons across the membrane from a region of low [H+] and negative electrical potential to a region of high [H+] and positive electrical potential. This establishes a proton gradient and a membrane potential that together form pmf. The crystal structures of the respiratory complexes succinate:ubiquinone oxidoreductase (SQR) and formate dehydrogenase-N (Fdh-N) from E. coli, have been solved to 2.6 and 1.6 Å respectively. The structures reveal detailed information about the structure/function relationship of each enzyme as well as demonstrating how pmf is generated. The aerobic respiratory complex SQR is a member of both the citric acid cycle and the respiratory chain. It oxidises succinate to fumarate in the cytoplasm and reduces ubiquinone in the membrane. SQR’s contribution to pmf is by reduction of ubiquinone to ubiquinol, which is subsequently used by other members of the respiratory chain to perform proton translocation. The structure of SQR reveals the location and properties of the ubiquinone binding site and helps explain why mutations in this region result in known diseases in higher organisms.Fdh-N, a member of a major anaerobic respiratory pathway in E. coli, forms a redox loop with dissimilatory nitrate reductase, linked by the menaquinone/menaquinol pool. This redox loop contributes to pmf by translocating two protons from the negative to the positive side and two electrons in the opposite direction. The structure of Fdh-N shows the molecular basis of this process and allows for the proposal of a quinone reduction mechanism.
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