title: 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 beta, gamma, and delta 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 delta subunit, these changes are themselves modified by mutations at the 9' position in other subunits. The data suggest an especially strong interaction between the beta and delta subunits in the pore region, leading in turn to a suggested arrangement of subunits within the pentamer.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Kearney
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Zhong
authors.forename: D A
authors.initials: DA
authors.lastname: Dougherty
authors.forename: H A
authors.initials: HA
authors.lastname: Lester
mesh_terms: D000818:Animals; D005260:Female; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D009865:Oocytes; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors; D014981:Xenopus
chemical_list: D007473:Ion Channels; D011978:Receptors, Nicotinic