TCB Publications - Abstract

Aleksij Aksimentiev, Ilya A. Balabin, Robert H. Fillingame, and Klaus Schulten. Insights into the molecular mechanism of rotation in the Fo sector of ATP synthase. Biophysical Journal, 86:1332-1344, 2004. (PMC: 1303972)

AKSI2004 $F_{1}$$F_{0}$-ATP synthase is a ubiquitous membrane protein complex that efficiently converts a cell's transmembrane proton gradient into chemical energy stored as ATP. The protein is made of two molecular motors, $F_{0}$ and $F_{1}$, which are coupled by a central stalk. The membrane unit, $F_{0}$, converts the transmembrane electrochemical potential into mechanical rotation of a rotor in $F_{0}$ and the physically connected central stalk. Based on available data of individual components, we have built an all-atom model of $F_{0}$ and investigated through molecular dynamics simulations and mathematical modeling the mechanism of torque generation in $F_{0}$. The mechanism that emerged generates the torque at the interface of the $a$ and $c$ subunits of $F_{0}$ through side groups $a$Ser206, $a$Arg210, $a$Asn214 of the $a$ subunit and side groups $c$Asp61 of the $c$ subunits. The mechanism couples protonation / deprotonation of two $c$Asp61, juxtaposed to the $a$ subunit at any moment in time, to rotations of individual $c$ subunit helices as well as rotation of the entire $c$ subunit. The $a$Arg210 side group orients the $c$Asp61 side groups and, thereby, establishes proton transfer via $a$Ser206 and $a$Asn214 to proton half-channels, while preventing direct proton transfer between the half-channels. A mathematical model proves the feasibility of torque generation by the stated mechanism against loads typical during ATP synthesis; the essential model characteristics, e.g., helix and subunit rotation and associated friction constants, have been tested and furnished by molecular dynamics simulations.

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