TY - JOUR
T1 - Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors
AU - Bouzat, Cecilia
AU - Bren, Nina
AU - Sine, Steven M.
N1 - Funding Information:
We thank Polly Quiram for technical contributions, Fred Sig-worth for providing the program VCATCH, and Marge Fynbo for contributions to the figures. This research was supported in part by National Institutes of Health grant NS31744 to S. M. S.
PY - 1994/12
Y1 - 1994/12
N2 - Structure-function studies have identified key functional motifs in the acetylcholine receptor, including residues that contribute to the ion channel and to the ligand-binding sites. Little is known, however, about determinants of channel gating kinetics. To identify structural correlates of gating, we examined the structual basis of the fetal-to-adult decrease in channel open time conferred by the presence of the s subunit in place of the γ subunit. By constructing chimeras composed of segments of the ε{lunate} and γ subunits, we show that the main determinant of this kinetic change is a 30 residue segment of a predicted amphipathic helix located between transmembrane domains M3 and M4. Further subdividing the amphipathic helix revealed that either multiple residues or its overall conformation confers this regulation of channel kinetics. We also show that L440 and M442, conserved residues within M4 of the γ subunit, contribute to long duration openings characteristic of the fetal receptor.
AB - Structure-function studies have identified key functional motifs in the acetylcholine receptor, including residues that contribute to the ion channel and to the ligand-binding sites. Little is known, however, about determinants of channel gating kinetics. To identify structural correlates of gating, we examined the structual basis of the fetal-to-adult decrease in channel open time conferred by the presence of the s subunit in place of the γ subunit. By constructing chimeras composed of segments of the ε{lunate} and γ subunits, we show that the main determinant of this kinetic change is a 30 residue segment of a predicted amphipathic helix located between transmembrane domains M3 and M4. Further subdividing the amphipathic helix revealed that either multiple residues or its overall conformation confers this regulation of channel kinetics. We also show that L440 and M442, conserved residues within M4 of the γ subunit, contribute to long duration openings characteristic of the fetal receptor.
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U2 - 10.1016/0896-6273(94)90424-3
DO - 10.1016/0896-6273(94)90424-3
M3 - Article
C2 - 7993630
AN - SCOPUS:0028600111
VL - 13
SP - 1395
EP - 1402
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -