期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：43
页码：13231-13236
DOI：10.1073/pnas.1517542112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceATP, the fuel of life, is produced in living cells by a complex molecular machine consisting of two motors linked by a rotor. One motor generates rotation by consuming energy derived from oxidative metabolism or photosynthesis; the other uses energy transmitted by the rotor to put ATP molecules together from their building blocks, ADP and phosphate. One such intact machine from the -proteobacterium Paracoccus denitrificans has been induced to form crystals, providing the means of deducing a blueprint of the machine, giving details of how its components are organized, and providing insights into how it works. The mechanistic principles deduced from the bacterial machine apply to similar molecular machines found in all living organisms. The structure of the intact ATP synthase from the -proteobacterium Paracoccus denitrificans, inhibited by its natural regulatory {zeta}-protein, has been solved by X-ray crystallography at 4.0 [IMG]f1.gif" ALT="A" BORDER="0"> resolution. The {zeta}-protein is bound via its N-terminal -helix in a catalytic interface in the F1 domain. The bacterial F1 domain is attached to the membrane domain by peripheral and central stalks. The {delta}-subunit component of the peripheral stalk binds to the N-terminal regions of two -subunits. The stalk extends via two parallel long -helices, one in each of the related b and b' subunits, down a noncatalytic interface of the F1 domain and interacts in an unspecified way with the a-subunit in the membrane domain. The a-subunit lies close to a ring of 12 c-subunits attached to the central stalk in the F1 domain, and, together, the central stalk and c-ring form the enzyme's rotor. Rotation is driven by the transmembrane proton-motive force, by a mechanism where protons pass through the interface between the a-subunit and c-ring via two half-channels in the a-subunit. These half-channels are probably located in a bundle of four -helices in the a-subunit that are tilted at [~]30{degrees} to the plane of the membrane. Conserved polar residues in the two -helices closest to the c-ring probably line the proton inlet path to an essential carboxyl group in the c-subunit in the proton uptake site and a proton exit path from the proton release site. The structure has provided deep insights into the workings of this extraordinary molecular machine.
