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Nicotinic Receptor Binding Site Probed with Unnatural Amino Acid Incorporation in Intact Cells

Nowak, Mark W. and Kearney, Patrick C. and Sampson, Jeffrey R. and Saks, Margaret E. and Labarca, Cesar G. and Silverman, Scott K. and Zhong, Wenge and Thorson, Jon and Abelson, John N. and Davidson, Norman and Schultz, Peter G. and Dougherty, Dennis A. and Lester, Henry A. (1995) Nicotinic Receptor Binding Site Probed with Unnatural Amino Acid Incorporation in Intact Cells. Science, 268 (5209). pp. 439-442. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20150120-140412390

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Abstract

The nonsense codon suppression method for unnatural amino acid incorporation has been applied to intact cells and combined with electrophysiological analysis to probe structure-function relations in the nicotinic acetylcholine receptor. Functional receptors were expressed in Xenopus oocytes when tyrosine and phenylalanine derivatives were incorporated at positions 93, 190, and 198 in the binding site of the α subunit. Subtle changes in the structure of an individual side chain produced readily detectable changes in the function of this large channel protein. At each position, distinct features of side chain structure dominated the dose-response relation, probably by governing the agonist-receptor binding.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.7716551 DOIArticle
http://www.sciencemag.org/content/268/5209/439PublisherArticle
ORCID:
AuthorORCID
Dougherty, Dennis A.0000-0003-1464-2461
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1995 American Association for the Advancement of Science. November 1994; accepted 23 January 1995. We thank V. Cornish, P. Deshpande, O. Uhlenbeck, and Y. Zhang for suggestions; E. Chapman for help with synthesis; and J. Jankowski for help with the measurements. Sponsored by grants from NIH, the Office of Naval Research, the Howard Hughes Medical Institute, the University of California Tobacco-Related Disease Research Project, and the Beckman Institute at Caltech.
Funders:
Funding AgencyGrant Number
NIHUNSPECIFIED
Office of Naval Research (ONR)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
California Tobacco-Related Disease Research ProgramUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Issue or Number:5209
Record Number:CaltechAUTHORS:20150120-140412390
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150120-140412390
Official Citation:Nowak, M., Kearney, P., Sampson, Saks, M., Labarca, C., Silverman, S., . . . et, a. (1995). Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells. Science, 268(5209), 439-442. doi: 10.1126/science.7716551
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53893
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:21 Jan 2015 05:44
Last Modified:03 Oct 2019 07:53

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