Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells

Mark W. Nowak, Patrick C. Kearney, Jeffrey R. Sampson, Margaret Ellen Saks, Cesar G. Labarca, Scott K Silverman, Wenge Zhong, Jon Thorson, John N. Abelson, Norman Davidson, Peter G. Schultz, Dennis A. Dougherty, Henry A. Lester

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)439-442
Number of pages4
JournalScience
Volume268
Issue number5209
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Nonsense Codon
Nicotinic Receptors
Xenopus
Phenylalanine
Oocytes
Tyrosine
Binding Sites
Amino Acids
Proteins

ASJC Scopus subject areas

  • General

Cite this

Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells. / Nowak, Mark W.; Kearney, Patrick C.; Sampson, Jeffrey R.; Saks, Margaret Ellen; Labarca, Cesar G.; Silverman, Scott K; Zhong, Wenge; Thorson, Jon; Abelson, John N.; Davidson, Norman; Schultz, Peter G.; Dougherty, Dennis A.; Lester, Henry A.

In: Science, Vol. 268, No. 5209, 01.01.1995, p. 439-442.

Research output: Contribution to journalArticle

Nowak, MW, Kearney, PC, Sampson, JR, Saks, ME, Labarca, CG, Silverman, SK, Zhong, W, Thorson, J, Abelson, JN, Davidson, N, Schultz, PG, Dougherty, DA & Lester, HA 1995, 'Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells', Science, vol. 268, no. 5209, pp. 439-442. https://doi.org/10.1126/science.7716551
Nowak, Mark W. ; Kearney, Patrick C. ; Sampson, Jeffrey R. ; Saks, Margaret Ellen ; Labarca, Cesar G. ; Silverman, Scott K ; Zhong, Wenge ; Thorson, Jon ; Abelson, John N. ; Davidson, Norman ; Schultz, Peter G. ; Dougherty, Dennis A. ; Lester, Henry A. / Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells. In: Science. 1995 ; Vol. 268, No. 5209. pp. 439-442.
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