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 involves allosteric communication between the membrane pore SecYEG and the associated SecA ATPase. Using singlemolecule fluorescence we reveal that slow conformational changes associated with the ATPase SecA modulate fast opening and closure of the SecY lateral gate. Such a mismatch of timescales is not compatible with direct coupling between SecA and SecYEG. A dynamic allosteric model is proposed in which the SecA ATPase cycle ‘steers’ the energy landscape for SecY pore opening. We map the experimental traces onto reduced reaction coordinates derived from molecular dynamics trajectories, providing a model for the energy landscape and a structural interpretation of the associated dynamics. Dynamic allostery may be common among motor ATPases that drive conformational changes in molecular machines.
Graphical TOC Entry
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* E-mail: ian.collinson{at}bristol.ac.uk; r.tuma{at}leeds.ac.uk
Additional fluorescence lifetime data provided in the supplement. Supplementary figures renumbered to accommodate additional data. Small edits to main Figures. Added discussion of transition path times in relation to protein folding events.