CaltechAUTHORS
  A Caltech Library Service

Establishing an Ion Pair Interaction in the Homomeric {rho}1 {gamma}-Aminobutyric Acid Type A Receptor That Contributes to the Gating Pathway

Wang, Jinti and Lester, Henry A. and Dougherty, Dennis A. (2007) Establishing an Ion Pair Interaction in the Homomeric {rho}1 {gamma}-Aminobutyric Acid Type A Receptor That Contributes to the Gating Pathway. Journal of Biological Chemistry, 282 (36). pp. 26210-26216. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:WANjbc07

[img]
Preview
PDF - Published Version
See Usage Policy.

645Kb
[img]
Preview
PDF - Supplemental Material
See Usage Policy.

203Kb

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:WANjbc07

Abstract

{gamma}-Aminobutyric acid type A (GABAA) receptors are members of the Cys-loop superfamily of ligand-gated ion channels. Upon agonist binding, the receptor undergoes a structural transition from the closed to the open state, but the mechanism of gating is not well understood. Here we utilized a combination of conventional mutagenesis and the high precision methodology of unnatural amino acid incorporation to study the gating interface of the human homopentameric {rho}1 GABAA receptor. We have identified an ion pair interaction between two conserved charged residues, Glu92 in loop 2 of the extracellular domain and Arg258 in the pre-M1 region. We hypothesize that the salt bridge exists in the closed state by kinetic measurements and free energy analysis. Several other charged residues at the gating interface are not critical to receptor function, supporting previous conclusions that it is the global charge pattern of the gating interface that controls receptor function in the Cys-loop superfamily.


Item Type:Article
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 2007 the American Society for Biochemistry and Molecular Biology. Received for publication, March 16, 2007, and in revised form, May 30, 2007. Originally published In Press as doi:10.1074/jbc.M702314200 on July 2, 2007 We thank Michael Torrice for the preparation of Nha. This work was supported by National Institutes of Health Grants NS 34407 and NS 11756. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.
Funders:
Funding AgencyGrant Number
NIHNS 34407
NIHNS 11756
Issue or Number:36
Record Number:CaltechAUTHORS:WANjbc07
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:WANjbc07
Alternative URL:http://dx.doi.org/:10.1074/jbc.M702314200
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8655
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:02 Sep 2007
Last Modified:04 Nov 2016 00:10

Repository Staff Only: item control page