title: Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors.
abstract: 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 structural basis of the fetal-to-adult decrease in channel open time conferred by the presence of the epsilon subunit in place of the gamma subunit. By constructing chimeras composed of segments of the epsilon and gamma 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 gamma subunit, contribute to long duration openings characteristic of the fetal receptor.
authors.affiliation: Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905.
authors.forename: C
authors.initials: C
authors.lastname: Bouzat
authors.forename: N
authors.initials: N
authors.lastname: Bren
authors.forename: S M
authors.initials: SM
authors.lastname: Sine
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004553:Electric Conductivity; D005333:Fetus; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D017433:Protein Structure, Secondary; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D008565:Membrane Proteins; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins