title: Molecular dissection of purinergic P2X receptor channels.
abstract: The P2X receptors (P2XRs) are a family of ATP-gated channels expressed in the plasma membrane of numerous excitable and nonexcitable cells and play important roles in control of cellular functions, such as neurotransmission, hormone secretion, transcriptional regulation, and protein synthesis. P2XRs are homomeric or heteromeric proteins, formed by assembly of at least three of seven subunits named P2X(1)-P2X(7). All subunits possess intracellular N- and C-termini, two transmembrane domains, and a relatively large extracellular ligand-binding loop. ATP binds to still an unidentified extracellular domain, leading to a sequence of conformational transitions between closed, open, and desensitized states. Removal of extracellular ATP leads to deactivation and resensitization of receptors. Activated P2XRs generate inward currents caused by Na(+) and Ca(2+) influx through the pore of channels, and thus mediate membrane depolarization and facilitation of voltage-gated calcium entry in excitable cells. No crystal structures are available for P2XRs and these receptors have no obvious similarity to other ion channels or ATP binding proteins, which limits the progress in understanding the relationship between molecular structure and conformational transitions of receptor in the presence of agonist and after its washout. We summarize here the alternative approaches in studies on molecular properties of P2XRs, including heteromerization, chimerization, mutagenesis, and biochemical studies.
authors.affiliation: Section on Cellular Signaling, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. stankos@helix.nih.gov
authors.forename: Stanko S
authors.initials: SS
authors.lastname: Stojilkovic
authors.forename: Melanija
authors.initials: M
authors.lastname: Tomic
authors.forename: Mu-Lan
authors.initials: ML
authors.lastname: He
authors.forename: Zonghe
authors.initials: Z
authors.lastname: Yan
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Koshimizu
authors.forename: Hana
authors.initials: H
authors.lastname: Zemkova
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002678:Chimera; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D008024:Ligands; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D007473:Ion Channels; D008024:Ligands; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate