Coupling H+ transport to rotary catalysis in F-type ATP synthases: Structure and organization of the transmembrane rotary motor

H+-transporting F1Fo-type ATP synthases utilize a transmembrane Hf potentia l 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 th e F-1 molecule between the alternating catalytic sites. The H+ electrochemi cal potential is thought to drive gamma subunit rotation by first coupling H+ transport to rotation of an oligomeric rotor of c subunits within the tr ansmembrane 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 o n the Escherichia coli F-o sector. The monomeric structure of subunit c, de termined by nuclear magnetic resonance (NMR), is discussed first and used a s a basis for the rest of the review. A model for the structural organizati on of the c(12) oligomer in F-o, deduced from extensive cross-linking studi es and by molecular modeling, is then described. The interactions between t he 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 subun it a (aTMH-4) and transmembrane helix 2 of subunit c (cTMH-2) during the pr oton-release step from Asp61 on cTMH-2 is suggested. Current a-c cross-link ing data can only be explained by helix-helix swiveling or rotation during the proton transfer steps. A model that mechanically links helix rotation w ithin a single subunit c to the incremental 30 degrees rotation of the c(12 ) oligomer is proposed. In the final section, the structural interactions b etween 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 p roposed on the basis of cross-linking data and the NMR structures of the in dividual subunits.