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Evidence for an Extended Hydrogen Bond Network in the Binding Site of the Nicotinic Receptor

Blum, Angela P. and Gleitsman, Kristin Rule and Lester, Henry A. and Dougherty, Dennis A. (2011) Evidence for an Extended Hydrogen Bond Network in the Binding Site of the Nicotinic Receptor. Journal of Biological Chemistry, 286 (37). pp. 32251-32258. ISSN 0021-9258. PMCID PMC3173184. https://resolver.caltech.edu/CaltechAUTHORS:20111004-120511603

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Abstract

The defining feature of the α subunits of the family of nicotinic acetylcholine receptors is a vicinal disulfide between Cys-192 and Cys-193. Although this structure has played a pivotal role in a number of pioneering studies of nicotinic receptors, its functional role in native receptors remains uncertain. Using mutant cycle analysis and unnatural residue mutagenesis, including backbone mutagenesis of the peptide bond of the vicinal disulfide, we have established the presence of a network of hydrogen bonds that extends from that peptide NH, across a β turn to another backbone hydrogen bond, and then across the subunit interface to the side chain of a functionally important Asp residue in the non-α subunit. We propose that the role of the vicinal disulfide is to distort the β turn and thereby properly position a backbone NH for intersubunit hydrogen bonding to the key Asp.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1074/jbc.M111.254235DOIArticle
http://www.jbc.org/content/286/37/32251.abstractPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173184/PubMed CentralArticle
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 2011 American Society for Biochemistry and Molecular Biology, Inc. Received for publication, April 25, 2011, and in revised form, July 8, 2011 Published, JBC Papers in Press, July 13, 2011. This work was supported, in whole or in part, by National Institutes of Health Grants NS 34407 (to D. A. D.) and NS 11756 (to H. A. L.).
Funders:
Funding AgencyGrant Number
NIHNS 34407
NIHNS 11756
Subject Keywords:Ion channels; Mutant; Nicotinic Acetylcholine Receptors; Protein Chemistry; Protein-Drug Interactions
Issue or Number:37
PubMed Central ID:PMC3173184
Record Number:CaltechAUTHORS:20111004-120511603
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20111004-120511603
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25637
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:04 Oct 2011 21:37
Last Modified:03 Oct 2019 03:07

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