A molecular dynamics study on the resilience of Sec61 channel from open to closed state

When the nascent chain is released from the ribosome, its packing into the apolar environment of the lipid bilayer in the endoplasmic reticulum is facilitated by the Sec61 translocon. In this process, coupling of the conformational change of the channel is essential to transport the nascent chain and meanwhile maintain the membrane permeability barrier. Two molecular dynamics simulations were performed in the current work to investigate the resilience of the lateral gate and the linkage mechanism of the lateral gate, pore ring and plug. The results affirmed that the lateral gate is able to recover its partially-closed state rapidly after the nascent chain segment enters the bilayer. This triggers subsequent motions of the pore ring and plug, which prevent the small molecules passing through the pore. The pore diameter in the partially-closed state is about 6–7 Å. The plug would move upward ∼2 Å if the lateral gate could not close. Two waters permeate through the channel when the lateral gate was open. Water molecules could go across the bilayer via the gap of the open lateral gate due to the occluding of the pore ring and plug.