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. doi:10.1126/science.7716551. 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.
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| 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. | ||||||||||||
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| Issue or Number: | 5209 | ||||||||||||
| DOI: | 10.1126/science.7716551 | ||||||||||||
| 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: | INVALID USER | ||||||||||||
| Deposited On: | 21 Jan 2015 05:44 | ||||||||||||
| Last Modified: | 10 Nov 2021 20:08 |
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