title: Comparative models of P2X2 receptor support inter-subunit ATP-binding sites.
abstract: ATP-gated P2X receptors (P2XRs) are ligand-gated ion channels (LGICs) presumably trimeric. To date, no experimental high-resolution structures are available. Recent X-ray structure of the acid-sensing ion channel 1 (ASIC1) revealed an unexpected trimeric ion channel. Beside their quaternary structure, P2XR and ASIC1 share common membrane topologies, but no significant sequence similarity. In order to overcome this low sequence resemblance, we have developed comparative models of P2X(2)R based on secondary structure predictions using the crystal structure of ASIC1 as template. These models were constrained to be consistent with known arrangement of disulfide bridges. They agreed with cross-linking experiments and supported inter-subunit ATP-binding sites. One of our models reconciled most existing data and provides new structural insights for a plausible mechanism of gating, thus encouraging new experiments.
authors: Department of Bioorganic Chemistry, UMR 7175 CNRS, Faculté de Pharmacie, Université Louis Pasteur, 67401 Illkirch, France.
authors: Guillaume
authors: G
authors: Guerlet
authors: Antoine
authors: A
authors: Taly
authors: Lia
authors: L
authors: Prado de Carvalho
authors: Adeline
authors: A
authors: Martz
authors: Ruotian
authors: R
authors: Jiang
authors: Alexandre
authors: A
authors: Specht
authors: Nicolas
authors: N
authors: Le Novère
authors: Thomas
authors: T
authors: Grutter
mesh_terms: D062565:Acid Sensing Ion Channels; D000255:Adenosine Triphosphate / Q000737:chemistry*; D001665:Binding Sites; D015640:Ion Channel Gating; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D018048:Receptors, Purinergic P2 / Q000737:chemistry*; D058476:Receptors, Purinergic P2X2; D015222:Sodium Channels / Q000737:chemistry
chemical_list: D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D015222:Sodium Channels; D000255:Adenosine Triphosphate