Fillingame R H, Jiang W, Dmitriev O Y, Jones P C
Department of Biomolecular Chemistry, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA.
Biochim Biophys Acta. 2000 May 31;1458(2-3):387-403. doi: 10.1016/s0005-2728(00)00089-x.
F(1)F(0) ATP synthases are known to synthesize ATP by rotary catalysis in the F(1) sector of the enzyme. Proton translocation through the F(0) membrane sector is now proposed to drive rotation of an oligomer of c subunits, which in turn drives rotation of subunit gamma in F(1). The primary emphasis of this review will be on recent work from our laboratory on the structural organization of F(0), which proves to be consistent with the concept of a c(12) oligomeric rotor. From the NMR structure of subunit c and cross-linking studies, we can now suggest a detailed model for the organization of the c(12) oligomer in F(0) and some of the transmembrane interactions with subunits a and b. The structural model indicates that the H(+)-carrying carboxyl of subunit c is located between subunits of the c(12) oligomer and that two c subunits pack in a front-to-back manner to form the proton (cation) binding site. The proton carrying Asp61 side chain is occluded between subunits and access to it, for protonation and deprotonation via alternate entrance and exit half-channels, requires a swiveled opening of the packed c subunits and stepwise association with different transmembrane helices of subunit a. We suggest how some of the structural information can be incorporated into models of rotary movement of the c(12) oligomer during coupled synthesis of ATP in the F(1) portion of the molecule.
已知F(1)F(0) ATP合酶通过酶的F(1)部分中的旋转催化来合成ATP。现在有人提出,质子通过F(0)膜部分的转运驱动c亚基寡聚体的旋转,而这又反过来驱动F(1)中γ亚基的旋转。本综述的主要重点将是我们实验室最近关于F(0)结构组织的研究工作,事实证明这与c(12)寡聚体转子的概念是一致的。根据亚基c的核磁共振结构和交联研究,我们现在可以提出一个关于F(0)中c(12)寡聚体组织以及与亚基a和b的一些跨膜相互作用的详细模型。结构模型表明,亚基c的携带H(+)的羧基位于c(12)寡聚体的亚基之间,并且两个c亚基以前后方式堆积形成质子(阳离子)结合位点。携带质子的天冬氨酸61侧链被封闭在亚基之间,要通过交替的入口和出口半通道对其进行质子化和去质子化,需要堆积的c亚基进行旋转打开,并与亚基a的不同跨膜螺旋逐步结合。我们提出了如何将一些结构信息纳入分子F(1)部分中ATP偶联合成过程中c(12)寡聚体旋转运动模型的方法。