Conformational Transition Of The Sec Translocon Induced By Channel Partner: A Molecular Dynamics Study

Sec translocon is a highly conserved heteromeric membrane protein complex, which functions as a protein-conducting channel. In bacteria, the Sec translocon (SecYEG) achieves the translocation of polypeptides across the membrane by binding of the channel partner, SecA ATPase. However, little is known about the atomically detailed mechanism on the translocation. Recently, a new crystal structure of the SecYE translocon bound with an anti-SecY Fab fragment has been determined. It contains a large hydrophobic crevasse open to the cytoplasm (the pre-open form) and differ from the crystal structure of SecYEβ from Methanococcus jannaschii in the closed form, suggesting that the binding of a channel partner induces a large conformational change of the Sec translocon in the initial step of the polypeptide translocation. To investigate the role of channel-partner binding to the SecYE translocon, we performed all-atom molecular dynamics simulations of SecYE with and without a Fab fragment in explicit membrane. During a 100-ns simulation, SecYE undergoes a large conformational transition toward the closed form in the absence of a Fab fragment, whereas the structure keeps the widely opened crevasse in the simulation of SecYE with a Fab fragment. In the transition, protein-lipid interaction around the lateral gate region of SecYE is changed greatly, indicating that there is a competition of interactions between the protein and phospholipid molecules, which is controlled by the binding of the channel partner to the SecYE transolon.