Energy landscape steering in SecYEG mediates dynamic coupling in ATP driven protein translocation

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 SecA and 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.