title: New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor.
abstract: The adenosine-5'-triphosphate (ATP) molecule is an extracellular messenger in neural and non-neural tissues, where it activates several cell-surface-receptor subtypes, including G-protein-coupled receptors and ligand-gated ion channels. ATP-gated channels (termed P2x receptors) have been characterized on smooth muscle cells and autonomic and sensory neurons, where they mediate membrane depolarization and, in some cases, Ca2+ entry. P2x receptors are functionally heterogeneous, but resemble acetylcholine- and serotonin-gated channels with respect to ion selectivity and kinetic parameters of channel gating. We report here that despite such close functional similarities, the deduced sequence of a cloned P2x receptor predicts an unusual subunit structure resembling voltage-insensitive cation channels. Thus, the P2x receptor provides a striking example of convergent evolution, whereby proteins have been fashioned with similar functional properties from subunits having very different structural characteristics. There is sequence similarity between the ATP receptor and RP-2, a gene activated in thymocytes undergoing programmed cell death. RP-2 may encode a receptor for ATP or another metabolite released during apoptosis.
authors.affiliation: Department of Pharmacology, University of California, San Francisco 94143-0450.
authors.forename: A J
authors.initials: AJ
authors.lastname: Brake
authors.forename: M J
authors.initials: MJ
authors.lastname: Wagenbach
authors.forename: D
authors.initials: D
authors.lastname: Julius
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D005075:Biological Evolution; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA; D004594:Electrophysiology; D005136:Eye Proteins; D019204:GTP-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009865:Oocytes; D016716:PC12 Cells; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014981:Xenopus
chemical_list: D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C072178:RP2 protein, human; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D004247:DNA; D019204:GTP-Binding Proteins