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

Biochemical and Biophysical Research Communications
Guillaume GuerletThomas Grutter

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.

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Citations

Sep 20, 2012·Chemical Reviews·Damien LemoineThomas Grutter
Jan 23, 2010·The Journal of Biological Chemistry·Sebastian KracunBaljit S Khakh
Feb 24, 2011·The Journal of Biological Chemistry·Amulya Nidhi ShrivastavaIsabella Sarto-Jackson
Jun 18, 2014·Journal of Molecular Biology·Stephan Kellenberger, Thomas Grutter
Oct 20, 2009·Trends in Biochemical Sciences·Mark T Young

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