Fillingame R H, Jiang W, Dmitriev O Y
Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA.
J Exp Biol. 2000 Jan;203(Pt 1):9-17. doi: 10.1242/jeb.203.1.9.
H(+)-transporting F(1)F(o)-type ATP synthases utilize a transmembrane H(+) potential to drive ATP formation by a rotary catalytic mechanism. ATP is formed in alternating beta subunits of the extramembranous F(1) sector of the enzyme, synthesis being driven by rotation of the gamma subunit in the center of the F(1) molecule between the alternating catalytic sites. The H(+) electrochemical potential is thought to drive gamma subunit rotation by first coupling H(+) transport to rotation of an oligomeric rotor of c subunits within the transmembrane F(o) sector. The gamma subunit is forced to turn with the c(12) oligomeric rotor as a result of connections between subunit c and the gamma and epsilon subunits of F(1). In this essay, we will review recent studies on the Escherichia coli F(o) sector. The monomeric structure of subunit c, determined by nuclear magnetic resonance (NMR), is discussed first and used as a basis for the rest of the review. A model for the structural organization of the c(12) oligomer in F(o), deduced from extensive cross-linking studies and by molecular modeling, is then described. The interactions between the the a(1)b(2) 'stator' subcomplex of F(o) and the c(12) oligomer are then considered. A functional interaction between transmembrane helix 4 of subunit a (aTMH-4) and transmembrane helix 2 of subunit c (cTMH-2) during the proton-release step from Asp61 on cTMH-2 is suggested. Current a-c cross-linking data can only be explained by helix-helix swiveling or rotation during the proton transfer steps. A model that mechanically links helix rotation within a single subunit c to the incremental 30 degrees rotation of the c(12) oligomer is proposed. In the final section, the structural interactions between the surface residues of the c(12) oligomer and subunits epsilon and gamma are considered. A molecular model for the binding of subunit epsilon between the exposed, polar surfaces of two subunits c in the oligomer is proposed on the basis of cross-linking data and the NMR structures of the individual subunits.
H(+)转运型F(1)F(o)型ATP合酶利用跨膜H(+)电位，通过旋转催化机制驱动ATP的形成。ATP在该酶膜外F(1)扇区的交替β亚基中形成，其合成由位于F(1)分子中心的γ亚基在交替催化位点之间的旋转驱动。H(+)电化学电位被认为通过首先将H(+)转运与跨膜F(o)扇区内c亚基的寡聚转子的旋转偶联来驱动γ亚基旋转。由于亚基c与F(1)的γ和ε亚基之间的连接，γ亚基被迫与c(12)寡聚转子一起转动。在本文中，我们将综述最近关于大肠杆菌F(o)扇区的研究。首先讨论通过核磁共振（NMR）确定的亚基c的单体结构，并将其用作本文其余部分的基础。然后描述了通过广泛的交联研究和分子建模推导得出的F(o)中c(12)寡聚体的结构组织模型。接着考虑F(o)的a(1)b(2)“定子”亚复合体与c(12)寡聚体之间的相互作用。有人提出，在质子从cTMH-2上的Asp61释放的步骤中，亚基a的跨膜螺旋4（aTMH-4）与亚基c的跨膜螺旋2（cTMH-2）之间存在功能相互作用。目前的a-c交联数据只能通过质子转移步骤中的螺旋-螺旋旋转或转动来解释。提出了一个将单个亚基c内的螺旋旋转与c(12)寡聚体的30度增量旋转机械连接的模型。在最后一部分中，考虑了c(12)寡聚体的表面残基与ε和γ亚基之间的结构相互作用。基于交联数据和各个亚基的NMR结构，提出了一个关于ε亚基在寡聚体中两个亚基c的暴露极性表面之间结合的分子模型。
