Energy landscape steering mediates dynamic coupling in ATP-driven protein translocation by the bacterial Sec machinery

Abstract

The Sec translocon is a transmembrane assembly highly conserved among all forms of life as the principal route for transport of polypeptides across or into lipid bilayers.In bacteria translocation is driven by allosteric communication between the membrane pore SecYEG and the associated SecA ATPase. Using time-resolved single molecule fluorescence we reveal that slow conformational changes associated with SecA ATPase (~ 6 s -1 ) modulate fast opening and closure of the SecY pore (~ 175 s -1 ). Such mismatch of timescales is not compatible with direct coupling between SecAand SecYEG and the power stroke mechanism. A dynamic allosteric model in which SecA ATPase cycle controls energy landscape for SecY pore opening is proposed and consistent with the Brownian-ratchet mechanism. Analysis of structures and molecular dynamics trajectories identified key molecular interactions involved in the mechanism. This dynamic allostery may be common among motor ATPases that drive conformational changes in molecular machines.A fascinating class of biological molecular machines are those operating upon biopolymer substrates and converting chemical energy derived from ATP binding and hydrolysis into cycles of conformational changes and mechanical work (e.g. helicases, translocases,

Energy landscapes and dynamics of ion translocation through membrane transporters: a meeting ground for physics, chemistry, and biology

“…Such transport is carried out by specialized enzymes and transporters embedded in biological membranes. To the best of our knowledge, a fundamental analysis that develops an analytical framework using Gibbs energy landscape approaches for membrane transporters in biological membranes has not been done, although some computational studies using all-atom molecular dynamics simulations and recent experimental studies using fluorescence resonance energy transfer on a few systems are available, often only in preprint form [12][13][14][15][16]. An analytical study on membrane filtration and flow through porous media treating Darcy's permeability law by the landscapes approach has recently been published [17].…”