Comparative models of P2X2 receptor support inter-subunit ATP-binding sites.

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TitleComparative models of P2X2 receptor support inter-subunit ATP-binding sites.
Publication TypeJournal Article
Year of Publication2008
AuthorsGuerlet, G, Taly, A, Prado de Carvalho, L, Martz, A, Jiang, R, Specht, A, Le Novère, N, Grutter, T
JournalBiochem Biophys Res Commun
Date Published2008 Oct 24
KeywordsAcid Sensing Ion Channels, Adenosine Triphosphate, Binding Sites, Ion Channel Gating, Models, Molecular, Nerve Tissue Proteins, Protein Folding, Protein Structure, Secondary, Receptors, Purinergic P2, Receptors, Purinergic P2X2, Sodium Channels

<p>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.</p>

Alternate JournalBiochem. Biophys. Res. Commun.
PubMed ID18718445