4dw0: Difference between revisions
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==Crystal structure of the ATP-gated P2X4 ion channel in the closed, apo state at 2.9 Angstroms== | |||
<StructureSection load='4dw0' size='340' side='right'caption='[[4dw0]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4dw0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DW0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DW0 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dw0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dw0 OCA], [https://pdbe.org/4dw0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dw0 RCSB], [https://www.ebi.ac.uk/pdbsum/4dw0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dw0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/P2X4A_DANRE 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]<ref>PMID:28332633</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:22535247</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4dw0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ion channels 3D structures|Ion channels 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Gouaux E]] | |||
[[Category: Hattori M]] | |||