Fillingame R H
Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison 53706, USA.
J Exp Biol. 1997 Jan;200(Pt 2):217-24. doi: 10.1242/jeb.200.2.217.
Reversible, F1F0-type ATPases (also termed F-ATP synthases) catalyze the synthesis of ATP during oxidative phosphorylation. In animal cells, the enzyme traverses the inner mitochondrial membrane and uses the energy of an H+ electrochemical gradient, generated by electron transport, in coupling H+ translocation to ATP formation. Closely related enzymes are found in the plasma membrane of bacteria such as Escherichia coli, where the enzymes function reversibly depending upon nutritional circumstance. The F1F0-type enzymes are more distantly related to a second family of H(+)-translocating ATPases, the vacuolar-type or V-ATPases. Recent structural information has provided important hints as to how these enzymes couple H+ transport to the chemical work of ATP synthesis. The simplest F1F0-type enzymes, e.g. as in E. coli, are composed of eight types of subunits in an unusual stoichiometry of alpha 3 beta 3 gamma delta epsilon (F1) and a1b2c12 (F0). F1 extends from the membrane, with the alpha and beta subunits alternating around a central subunit gamma. ATP synthesis occurs alternately in different beta subunits, the cooperative tight binding of ADP + Pi at one catalytic site being coupled to ATP release at a second. The differences in binding affinities appear to be caused by rotation of the gamma subunit in the center of the alpha 3 beta 3 hexamer. The gamma subunit traverses a 4.5 nm stalk connecting the catalytic subunits to the membrane-traversing F0 sector. Subunit c is the H(+)-translocating subunit of F0. Protonation/deprotonation of Asp61 in the center of the membrane is coupled to structural changes in an extramembranous loop of subunit c which interacts with both the gamma and epsilon subunits. Subunits gamma and epsilon appear to move from one subunit c to another as ATP is synthesized. The torque of such movement is proposed to cause the rotation of gamma within the alpha 3 beta 3 complex. Four protons are translocated for each ATP synthesized. The movement of gamma and epsilon therefore probably involves a unit of four c subunits. The organization of subunits in F0 remains a mystery; it will have to be understood if we are to understand the mechanism of torque generation.
可逆的F1F0型ATP酶（也称为F - ATP合酶）在氧化磷酸化过程中催化ATP的合成。在动物细胞中，该酶穿过线粒体内膜，并利用电子传递产生的H⁺电化学梯度的能量，将H⁺转运与ATP的形成相偶联。在诸如大肠杆菌等细菌的质膜中发现了密切相关的酶，这些酶根据营养状况可逆地发挥作用。F1F0型酶与第二类H⁺转运ATP酶，即液泡型或V - ATP酶的关系更为疏远。最近的结构信息为这些酶如何将H⁺转运与ATP合成的化学过程相偶联提供了重要线索。最简单的F1F0型酶，例如大肠杆菌中的酶，由八种类型的亚基组成，其化学计量比异常，为α3β3γδε（F1）和a1b2c12（F0）。F1从膜上延伸出来，α和β亚基围绕中央亚基γ交替排列。ATP合成在不同的β亚基中交替发生，ADP + Pi在一个催化位点的协同紧密结合与ATP在另一个催化位点的释放相偶联。结合亲和力的差异似乎是由γ亚基在α3β3六聚体中心的旋转引起的。γ亚基穿过一个4.5纳米的柄，将催化亚基与穿过膜的F0部分连接起来。亚基c是F0的H⁺转运亚基。膜中心的Asp61的质子化/去质子化与亚基c的膜外环的结构变化相偶联，该膜外环与γ和ε亚基相互作用。随着ATP的合成，γ和ε亚基似乎从一个亚基c移动到另一个亚基c。这种运动的扭矩被认为会导致γ在α3β3复合物内旋转。每合成一个ATP，就有四个质子被转运。因此，γ和ε的运动可能涉及四个c亚基的一个单元。F0中亚基的组织仍然是个谜；如果我们要理解扭矩产生的机制，就必须弄清楚这一点。
