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4dw0

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Crystal structure of the ATP-gated P2X4 ion channel in the closed, apo state at 2.9 Angstroms

Structural highlights

4dw0 is a 1 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P2X4A_DANRE ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium (By similarity). CTP, but not GTP or UTP, functions as a weak affinity agonist for P2RX4 (PubMed:28332633). Activated by extracellularly released ATP, it plays multiple role in immunity and central nervous system physiology (By similarity). Could also function as an ATP-gated cation channel of lysosomal membranes (By similarity).[UniProtKB:P51577][UniProtKB:Q99571][UniProtKB:Q9JJX6]^[1]

Publication Abstract from PubMed

P2X receptors are trimeric ATP-activated ion channels permeable to Na+, K+ and Ca2+. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X4 receptor in complex with ATP and a new structure of the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body beta-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.

Molecular mechanism of ATP binding and ion channel activation in P2X receptors.,Hattori M, Gouaux E Nature. 2012 May 10;485(7397):207-12. PMID:22535247^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kasuya G, Fujiwara Y, Tsukamoto H, Morinaga S, Ryu S, Touhara K, Ishitani R, Furutani Y, Hattori M, Nureki O. Structural insights into the nucleotide base specificity of P2X receptors. Sci Rep. 2017 Mar 23;7:45208. doi: 10.1038/srep45208. PMID:28332633 doi:http://dx.doi.org/10.1038/srep45208
↑ Hattori M, Gouaux E. Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature. 2012 May 10;485(7397):207-12. PMID:22535247 doi:http://dx.doi.org/10.1038/nature11010