Determination of the structures of respiratory enzyme complexes from mammalian mitochondria.
Knowledge of the atomic resolution structures of the respiratory enzymes from mammalian mitochondria is likely to be essential for understanding the molecular basis of human diseases involving their dysfunction. Because they are membrane-bound multisubunit assemblies, the determination of their high resolution structures is a rather challenging undertaking. The greatest progress has been made with the ATP synthase. The structure of its catalytic domain, F1-ATPase, has been solved by X-ray crystallography at 2.8 A resolution. It supports a binding change mechanism of catalysis in intact ATP synthase in which the catalytic subunits are in different states of the catalytic cycle at any instant. Interconversion of the states may be achieved by rotation of an alpha-helical domain of the gamma-subunit relative to the alpha 3 beta 3 sub-assembly. The membrane domain of ATP synthase has been purified, and the stalk linking the catalytic and membrane domains has been reassembled in vitro from its constituent subunits. Considerable progress has also been made in analyzing the structure of bovine complex I. It has about 43 different subunits and 42 of them have been sequenced. All of the known prosthetic groups have been localized in its extrinsic membrane arm, which has been split away from the membrane subunits and purified. The next stage is to crystallize the domain and to solve its structure.
Walker
J E
JE
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D007425:Intracellular Membranes / Q000201:enzymology; D046911:Macromolecular Substances; D008322:Mammals; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry*; D017433:Protein Structure, Secondary; D006180:Proton-Translocating ATPases / Q000737:chemistry*
D046911:Macromolecular Substances; D016660:NAD(P)H Dehydrogenase (Quinone); D006180:Proton-Translocating ATPases