A single site on the epsilon subunit is responsible for the change in ACh receptor channel conductance during skeletal muscle development.
Four critically positioned amino acids on each of the alpha, beta, delta, and gamma subunits of the Torpedo nicotinic acetylcholine receptor are determinants of channel conductance. Our results show that the gamma and epsilon subunits of Xenopus muscle receptors are identical at all four positions, despite the fact that alpha 2 beta delta epsilon receptors have a 50% greater conductance than alpha 2 beta delta gamma receptors. Instead, the functional difference is conferred by a single charged residue that lies extracellular to all four positions, corresponding to a location in the Torpedo receptor previously shown to have no influence on conductance. Substitution of a positively charged lysine residue in gamma by the neutral methionine in epsilon at this extra-cellular position is responsible for the increased conductance during maturation of the amphibian neuromuscular junction.
Murray
N
N
Department of Neurobiology and Behavior, State University of New York at Stony Brook 11794, USA.
Zheng
Y C
YC
Mandel
G
G
Brehm
P
P
Bolinger
R
R
Reuer
Q
Q
Kullberg
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004553:Electric Conductivity; D004563:Electrochemistry; D005260:Female; D007700:Kinetics; D007814:Larva / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000502:physiology; D016296:Mutagenesis; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014101:Torpedo; D014981:Xenopus / Q000254:growth & development*
D046911:Macromolecular Substances; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D008239:Lysine