New structure enlivens interest in P2X receptors.
P2X receptors are ATP-gated membrane ion channels with multifarious roles, including afferent sensation, autocrine feedback loops, and inflammation. Their molecular operation has been less well elucidated compared with other ligand-gated channels (nicotinic acetylcholine receptors, ionotropic glutamate receptors). This will change with the recent publication of the crystal structure of a closed P2X receptor. Here we re-interpret results from 15 years of experiments using site-directed mutagenesis with a model based on the new structure. Previous predictions of receptor stoichiometry, the extracellular ATP binding site, inter-subunit contacts, and many details of the permeation pathway fall into place in three dimensions. We can therefore quickly understand how the channel operates at the molecular level. This is important not only for ion- channel aficionados, but also those engaged in developing effective antagonists at P2X receptors for potential therapeutic use.
Faculty of Medical and Human Sciences, University of Manchester, UK.
Liam E
LE
Browne
Lin-Hua
LH
Jiang
R Alan
RA
North
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed / Q000379:methods; D010539:Permeability; D011485:Protein Binding; D011487:Protein Conformation; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000378:metabolism*; D058469:Receptors, Purinergic P2X
D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate