Structure of P2X receptors

P2X receptors are trimeric ion channels that open in response to extracellular ATP. The publication of the first X-ray structure of a closed P2X receptor has confirmed many of the functional experiments carried out since the mid-1990s and provides a point of reference for the molecular dissection of P2X receptor function. These co-ordinates shed light on the ATP binding sites housed in the extracellular domain, the contacts between subunits, the pathways for ion access, and the cation-selective pore that spans the cell membrane. They also provide a template for structure-based design of much needed pharmacological agents to act on a receptor superfamily whose physiological roles extend from synaptic transmission to inflammation and control of programmed cell death. Interpretation of functional data in the context of this closed P2X receptor structure reveals structural rearrangements in the transmembrane pore and extracellular domain. Here the current understanding of the molecular structure of P2X receptors is reviewed. This review will be of relevance to those interested in the mechanisms that underlie the molecular operation of P2X receptors, and other ion channels gated by diffusible ligands (pentameric Cys-loop receptors, tetrameric glutamate receptors), as well as trimeric ion channels that are distantly related to P2X receptors (acid-sensing ion channels and the epithelial sodium channel). © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..