title: Molecular structure and function of P2X receptors.
abstract: ATP-gated P2X receptors are trimeric ion channels selective to cations. Recent progress in the molecular biophysics of these channels enables a better understanding of their function. In particular, data obtained from biochemical, electrophysiogical and molecular engineering in the light of recent X-ray structures now allow delineation of the principles of ligand binding, channel opening and allosteric modulation. However, although a picture emerges as to how ATP triggers channel opening, there are a number of intriguing questions that remain to be answered, in particular how the pore itself opens in response to ATP and how the intracellular domain, for which structural information is limited, moves during activation. In this review, we provide a summary of functional studies in the context of the post-structure era, aiming to clarify our understanding of the way in which P2X receptors function in response to ATP binding, as well as the mechanism by which allosteric modulators are able to regulate receptor function. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, F-67400, Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, F-67400, Illkirch, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Habermacher
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, F-67400, Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, F-67400, Illkirch, France.
authors.forename: Kate
authors.initials: K
authors.lastname: Dunning
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, F-67400, Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, F-67400, Illkirch, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Chataigneau
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, F-67400, Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, F-67400, Illkirch, France. Electronic address: grutter@unistra.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grutter
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D006801:Humans; D015640:Ion Channel Gating; D062308:Optogenetics; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D017434:Protein Structure, Tertiary; D058469:Receptors, Purinergic P2X / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate
keywords: ATP; ATP (PubChem CID: 5957); Allosteric modulation; GW791343 (PubChem CID: 71576670); Gating; Ion channel; Ivermectin (PubChem CID:24278497); Purinergic receptors; Suramin (PubChem CID: 5361); TNP-ATP (PubChem CID: 3035228)