Physical mechanisms of the Sec machinery operation

The Sec complex, composed of a motor protein SecA and a channel SecYEG, is an ATP-driven molecular machine for the transport of proteins across the plasma membrane in bacteria. Today, there is a consensus about a general "rough" model of the complex activation and operation, which, however, lacks understanding of the physical mechanisms behind it. Molecular dynamics simulations were employed to address a way of allosteric activation, conformational transition of SecYEG from the closed to the open state, and driving forces of protein transport. We found that binding of SecA (in the ATP-bound state) and the protein signal sequence leads to a transmembrane helix rearrangment that weakens contacts inside the hydrophobic core of SecYEG and provides a driving force for plug opening. The conformational transitions are enabled by a delicate interplay between hydrophobic forces on one side and PEES (proton motive force, external - due to binding with the translocation partners - entropic, and solvent-induced) on the other side. In the open state, SecYEG still provides a barrier for bulky residues that contributes to the driving forces of transport. Other important contributions come from SecA and the membrane potential acting in different stages of protein transport to guarantee a nearly constant driving force. Given that the different forces act on different types of residues, the suggested mechanisms taken together provide a directional motion for any substrate, thereby maximizing the efficiency of the Sec machinery.