CaltechAUTHORS
  A Caltech Library Service

Backbone Mutations in Transmembrane Domains of a Ligand-Gated Ion Channel: Implications for the Mechanism of Gating

England, Pamela M. and Zhang, Yinong and Dougherty, Dennis A. and Lester, Henry A. (1999) Backbone Mutations in Transmembrane Domains of a Ligand-Gated Ion Channel: Implications for the Mechanism of Gating. Cell, 96 (1). pp. 89-98. ISSN 0092-8674. doi:10.1016/s0092-8674(00)80962-9. https://resolver.caltech.edu/CaltechAUTHORS:20200514-152725398

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20200514-152725398

Abstract

An approach to identify backbone conformational changes underlying nicotinic acetylcholine receptor (nAChR) gating was developed. Specific backbone peptide bonds were replaced with an ester, which disrupts backbone hydrogen bonds at the site of mutation. At a conserved proline residue (αPro221) in the first transmembrane (M1) domain, the amide-to-ester mutation provides receptors with near-normal sensitivity, although the natural amino acids tested other than Pro produce receptors that gate with a much larger EC₅₀ than normal. Therefore, a backbone hydrogen bond at this site may interfere with normal gating. In the αM2 domain, the amide-to-ester mutation yielded functional receptors at 15 positions, 3 of which provided receptors with >10-fold lower EC₅₀ than wild type. These results support a model for gating that includes significant changes of backbone conformation within the M2 domain.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/s0092-8674(00)80962-9DOIArticle
ORCID:
AuthorORCID
Dougherty, Dennis A.0000-0003-1464-2461
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1999 Cell Press. Under an Elsevier user license. We thank Cesar Labarca for gathering some of the data on conventional mutants in the M1 domain; Hong Dang for sharing unpublished information concerning the α 7 receptor; Sonia Pollit and Peter Schultz for samples of leucic acid and pipecolic acid; and members of our laboratory for much discussion. This research was supported by grants from the NIH (grants NS11756 and NS34407) and by National Research Service Awards to P. M. E. and Y. Z.
Funders:
Funding AgencyGrant Number
NIHNS11756
NIHNS34407
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:1
DOI:10.1016/s0092-8674(00)80962-9
Record Number:CaltechAUTHORS:20200514-152725398
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200514-152725398
Official Citation:Pamela M. England, Yinong Zhang, Dennis A. Dougherty, Henry A. Lester, Backbone Mutations in Transmembrane Domains of a Ligand-Gated Ion Channel: Implications for the Mechanism of Gating, Cell, Volume 96, Issue 1, 1999, Pages 89-98, ISSN 0092-8674, https://doi.org/10.1016/S0092-8674(00)80962-9. (http://www.sciencedirect.com/science/article/pii/S0092867400809629)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103214
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 May 2020 22:37
Last Modified:16 Nov 2021 18:19

Repository Staff Only: item control page