title: Gating transition of pentameric ligand-gated ion channels.
abstract: Pentameric ligand-gated ion channels are an important family of membrane proteins and play key roles in physiological processes, including signal transduction at chemical synapses. Here, we study the conformational changes associated with the opening and closing of the channel pore. Based on recent crystal structures of two prokaryotic members of the family in open and closed states, respectively, mixed elastic network models are constructed for the transmembrane domain. To explore the conformational changes in the gating transition, a coarse-grained transition path is computed that smoothly connects the closed and open conformations of the channel. We find that the conformational transition involves no major rotations of the transmembrane helices, and is instead characterized by a concerted tilting of helices M2 and M3. In addition, helix M2 changes its bending state, which results in an early closure of the pore during the open-to-closed transition.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Fangqiang
authors.initials: F
authors.lastname: Zhu
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hummer
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D004548:Elasticity; D004594:Electrophysiology / Q000379:methods; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D007473:Ion Channels; D008024:Ligands; D008565:Membrane Proteins