Regions of beta 4.beta 2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors.
Fifteen chimeric nicotinic receptor beta subunits were constructed consisting of N-terminal neuronal beta 4 sequences and C-terminal beta 2 sequences. Responses to cytisine, nicotine, or tetramethylammonium were compared to acetylcholine responses for these subunits expressed in Xenopus oocytes with alpha 3 subunits. The results show that (i) two residues in the extracellular domain of chimeric beta 4.beta 2 subunits (108 beta 2F/beta 4V, 110 beta 2S/beta 4T) account for much of the relative cytisine sensitivity; and (ii) four extracellular residues of chimeric beta 4.beta 2 subunits (112 beta 2A/beta 4V, 113 beta 2V/beta 4I and 115 beta 2S/beta 4R, 116 beta 2Y/beta 4S) account for most of the relative tetramethylammonium sensitivity. The data did not permit localization of nicotine sensitivity to any particular region.
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Division of Chemistry, California Institute of Technology, Pasadena 91125.
Cohen
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Quick
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Davidson
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N
Lester
H A
HA
D000109:Acetylcholine / Q000378:metabolism; D000470:Alkaloids / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001392:Azocines; D004252:DNA Mutational Analysis; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism; D009865:Oocytes; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D011807:Quinolizines; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014981:Xenopus; D000093843:Quinolizidine Alkaloids
D000109:Acetylcholine; D000470:Alkaloids; D001392:Azocines; D009538:Nicotine; D000644:Quaternary Ammonium Compounds; D011807:Quinolizines; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C027917:tetramethylammonium