Coupling H+ Transport to Rotary Catalysis in F-Type ATP Synthases: Structure and Organization of the Transmembrane Rotary Motor

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Abstract
H+-transporting F1Fo-type ATP synthases utilize a transmembrane H+ potential to drive ATP formation by a rotary catalytic mechanism. ATP is formed in alternating β subunits of the extramembranous F1 sector of the enzyme, synthesis being driven by rotation of the γ subunit in the center of the F1 molecule between the alternating catalytic sites. The H+ electrochemical potential is thought to drive γ subunit rotation by first coupling H+ transport to rotation of an oligomeric rotor of c subunits within the transmembrane Fo sector. The γ subunit is forced to turn with the c12 oligomeric rotor as a result of connections between subunit c and the γ and ε subunits of F1. In this essay, we will review recent studies on the Escherichia coli Fo 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 c12 oligomer in Fo, deduced from extensive cross-linking studies and by molecular modeling, is then described. The interactions between the the a1b2 ‘stator’ subcomplex of Fo and the c12 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 ° rotation of the c12 oligomer is proposed. In the final section, the structural interactions between the surface residues of the c12 oligomer and subunits ε and γ are considered. A molecular model for the binding of subunit ε 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.