title: Plasticity of acetylcholine receptor gating motions via rate-energy relationships.
abstract: Like other protein conformational changes, ion channel gating requires the protein to achieve a high-energy transition-state structure. It is not known whether ion channel gating takes place on a broad energy landscape on which many alternative transition state structures are accessible, or on a narrow energy landscape where only a few transition-state structures are possible. To address this question, we measured how rate-equilibrium free energy relationships (REFERs) for di-liganded and unliganded acetylcholine receptor gating vary as a function of the gating equilibrium constant. A large slope for the REFER plot indicates an openlike transition state, whereas a small slope indicates a closedlike transition state. Due to this relationship between REFERs and transition-state structure, the sensitivity of the REFER slope to mutation-induced energetic perturbations allows estimation of the breadth of the energy landscape underlying gating. The relatively large sensitivity of di-liganded REFER slopes to energetic perturbations suggests that the motions underlying di-liganded gating take place on a broad, shallow energy landscape where many alternative transition-state structures are accessible.
authors.affiliation: Center for Single Molecule Biophysics and the Department of Physiology and Biophysics, The State University of New York, Buffalo, NY, USA.
authors.forename: Ananya
authors.initials: A
authors.lastname: Mitra
authors.forename: Richard
authors.initials: R
authors.lastname: Tascione
authors.forename: Anthony
authors.initials: A
authors.lastname: Auerbach
authors.forename: Stuart
authors.initials: S
authors.lastname: Licht
mesh_terms: D000818:Animals; D004594:Electrophysiology; D015640:Ion Channel Gating; D007473:Ion Channels; D007477:Ions; D007700:Kinetics; D008024:Ligands; D019563:Mechanics; D008564:Membrane Potentials; D051379:Mice; D008968:Molecular Conformation; D009038:Motion; D009154:Mutation; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D011487:Protein Conformation; D011950:Receptors, Cholinergic / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D007473:Ion Channels; D007477:Ions; D008024:Ligands; D011950:Receptors, Cholinergic