Structural determinants of lateral gate opening in the protein translocon.
The heterotrimeric SecY/Sec61 complex is a protein-conducting channel that provides a passage for proteins across the membrane as well as a means to integrate nascent proteins into the membrane. While the first function is common among membrane protein channels and transporters, the latter is unique. Insertion of nascent membrane proteins, one transmembrane segment at a time, by SecY likely occurs through a lateral gate in the channel. Molecular dynamics simulations have been used to investigate the mechanism of gate opening. Opening and closing the gate under different conditions allowed us to identify structural elements that resist opening as well as those that aid closure. SecE, considered to act as a clamp keeping the lateral gate closed, was found to play no such role. Loosening of the plug by lateral gate opening, a potential step in channel gating, was also observed. The simulations revealed that lipids on time scales of up to 1 micros do not flood channels with an open lateral gate.
Gumbart
James
J
Department of Physics, University of Illinois at Urbana-Champaign, Beckman Institute for Advanced Science and Technology, Urbana, Illinois 61801, USA.
Schulten
Klaus
K
D003198:Computer Simulation; D015640:Ion Channel Gating / Q000502:physiology*; D008563:Membrane Lipids / Q000737:chemistry; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D011487:Protein Conformation; D021381:Protein Transport / Q000502:physiology; D013816:Thermodynamics
D008563:Membrane Lipids; D026901:Membrane Transport Proteins