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Biochem Biophys Res Commun. 2008 Oct 24;375(3):405-9. doi: 10.1016/j.bbrc.2008.08.030. Epub 2008 Aug 19.

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

Author information

1
Department of Bioorganic Chemistry, UMR 7175 CNRS, Faculté de Pharmacie, Université Louis Pasteur, 67401 Illkirch, France.

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.

PMID:
18718445
DOI:
10.1016/j.bbrc.2008.08.030
[Indexed for MEDLINE]

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