Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1410K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jha, A. Articles by Auerbach, A. Search for Related Content PubMed PubMed Citation Articles by Jha, A. Articles by Auerbach, A. Related Collections Related Articles Social Bookmarking                      What's this?

Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214

Correspondence to Anthony Auerbach: auerbach{at}buffalo.edu

Acetylcholine receptor channel gating is a propagated conformational cascade that links changes in structure and function at the transmitter binding sites in the extracellular domain (ECD) with those at a "gate" in the transmembrane domain (TMD). We used -value analysis to probe the relative timing of the gating motions of -subunit residues located near the ECD–TMD interface. Mutation of four of the seven amino acids in the M2–M3 linker (which connects the pore-lining M2 helix with the M3 helix), including three of the four residues in the core of the linker, changed the diliganded gating equilibrium constant (K_eq) by up to 10,000-fold (P272 > I274 > A270 > G275). The average -value for the whole linker was 0.64. One interpretation of this result is that the gating motions of the M2–M3 linker are approximately synchronous with those of much of M2 (0.64), but occur after those of the transmitter binding site region (0.93) and loops 2 and 7 (0.77). We also examined mutants of six cys-loop residues (V132, T133, H134, F135, P136, and F137). Mutation of V132, H134, and F135 changed K_eq by 2800-, 10-, and 18-fold, respectively, and with an average -value of 0.74, similar to those of other cys-loop residues. Even though V132 and I274 are close, the energetic coupling between I and V mutants of these positions was small (0.51 kcal mol^–1). The M2–M3 linker appears to be the key moving part that couples gating motions at the base of the ECD with those in TMD. These interactions are distributed along an 16-Å border and involve about a dozen residues.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Articles

Acetylcholine Receptor Gating at Extracellular Transmembrane Domain Interface: the "Pre-M1" Linker

Prasad Purohit and Anthony Auerbach
J. Gen. Physiol. 2007 130: 559-568. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				W. Y. Lee, C. R. Free, and S. M. Sine Nicotinic Receptor Interloop Proline Anchors {beta}1-{beta}2 and Cys loops in Coupling Agonist Binding to Channel Gating J. Gen. Physiol., August 1, 2008; 132(2): 265 - 278. [Abstract] [Full Text] [PDF]

				C. Bouzat, M. Bartos, J. Corradi, and S. M. Sine The Interface between Extracellular and Transmembrane Domains of Homomeric Cys-Loop Receptors Governs Open-Channel Lifetime and Rate of Desensitization J. Neurosci., July 30, 2008; 28(31): 7808 - 7819. [Abstract] [Full Text] [PDF]

				P. Purohit and A. Auerbach Acetylcholine Receptor Gating at Extracellular Transmembrane Domain Interface: the "Pre-M1" Linker J. Gen. Physiol., November 26, 2007; 130(6): 559 - 568. [Abstract] [Full Text] [PDF]

				P. Purohit and A. Auerbach Acetylcholine Receptor Gating: Movement in the {alpha}-Subunit Extracellular Domain J. Gen. Physiol., November 26, 2007; 130(6): 569 - 579. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents