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

Mark W. Nowak; Patrick C. Kearney; Jeffrey R. Sampson; Margaret E. 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

doi:10.1126/science.7716551

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

Mark W. Nowak, Patrick C. Kearney, Jeffrey R. Sampson, Margaret E. 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 journal › Article › peer-review

214 Scopus citations

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 language	English
Pages (from-to)	439-442
Number of pages	4
Journal	Science
Volume	268
Issue number	5209
DOIs	https://doi.org/10.1126/science.7716551
State	Published - 1995

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title = "Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells",

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.",

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

year = "1995",

doi = "10.1126/science.7716551",

language = "English",

volume = "268",

pages = "439--442",

number = "5209",

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T1 - Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells

AU - Nowak, Mark W.

AU - Kearney, Patrick C.

AU - Sampson, Jeffrey R.

AU - Saks, Margaret E.

AU - Labarca, Cesar G.

AU - Silverman, Scott K.

AU - Zhong, Wenge

AU - Thorson, Jon

AU - Abelson, John N.

AU - Davidson, Norman

AU - Schultz, Peter G.

AU - Dougherty, Dennis A.

AU - Lester, Henry A.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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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JF - Science

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ER -

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

Abstract

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