Determinants of Nicotinic Receptor Gating in Natural and Unnatural Side Chain Structures at the M2 9′ Position
Abstract
A nonsense suppression method was employed to incorporate a total of four natural and six unnatural residues at the 9′ position of the M2 region in the β, γ, and δ subunits of muscle nicotinic receptors. In 33 pairwise comparisons of functional properties as influenced by structural features including side chain length, branching, and substitution of oxygen for methylene carbons, it is concluded that increased polarity in the side chains at the 9′ position consistently increases the sensitivity to acetylcholine. In addition, the stereochemistry of the side chain can have marked influences on the EC₅₀, primarily because of changes in the single-channel open time. For the case of isoleucine versus allo-isoleucine in the δ subunit, these changes are themselves modified by mutations at the 9′ position in other subunits. The data suggest an especially strong interaction between the β and δ subunits in the pore region, leading in turn to a suggested arrangement of subunits within the pentamer.
Additional Information
© 1996 Cell Press. Published by Elsevier Inc. Received 13 September 1996, Revised 16 October 1996. We thank Brad Henkle for help with oocytes and H. Dang, P. England, C. Labarca, M. Nowak, M. E. Saks, J. Sampson, S. Silverman, and Y. Zhang for comments. This work was supported by the National Institutes of Health (NS34407 and NS11756), by the California Tobacco-Related Disease Research Program, and by the Beckman Institute at Caltech. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.Additional details
- Eprint ID
- 103252
- Resolver ID
- CaltechAUTHORS:20200518-070216780
- NS34407
- NIH
- NS11756
- NIH
- California Tobacco-Related Disease Research Program
- Caltech Beckman Institute
- Created
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2020-05-18Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field