View source for 9ddv


==Cryo-EM structure of the human P2X2 receptor in the apo closed state==
<StructureSection load='9ddv' size='340' side='right'caption='[[9ddv]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ddv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9DDV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DDV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.71&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=9ddv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ddv OCA], [https://pdbe.org/9ddv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ddv RCSB], [https://www.ebi.ac.uk/pdbsum/9ddv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ddv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/P2RX2_HUMAN P2RX2_HUMAN] Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/P2RX2_HUMAN P2RX2_HUMAN] ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium (PubMed:10570044, PubMed:31636190). Activation by extracellular ATP induces a variety of cellular responses, such as excitatory postsynaptic responses in sensory neurons, neuromuscular junctions (NMJ) formation, hearing, perception of taste and peristalsis (By similarity). In the inner ear, regulates sound transduction and auditory neurotransmission, outer hair cell electromotility, inner ear gap junctions, and K(+) recycling (PubMed:23345450). Mediates synaptic transmission between neurons and from neurons to smooth muscle (By similarity).[UniProtKB:Q8K3P1]<ref>PMID:10570044</ref> <ref>PMID:23345450</ref> <ref>PMID:31636190</ref> 
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== Publication Abstract from PubMed ==
The P2X2 receptor (P2X2R) is a slowly desensitizing adenosine triphosphate (ATP)-gated ion channel that is highly expressed in the cochlea. When mutated, the P2X2R exacerbates age- and noise-related hearing loss, but selective modulators of the receptor are lacking, and the molecular basis of activation and desensitization remains poorly understood. Here, we determine high-resolution cryoelectron microscopy structures of the full-length wild-type human P2X2R in an apo closed state and two distinct ATP-bound desensitized states. In the apo closed state structure, we observe features unique to the P2X2R and locate disease mutations within or near the transmembrane domain. In addition, our ATP-bound structures show how free anionic ATP forms subtype-specific interactions with the orthosteric binding site. We identify and characterize two different ATP-bound desensitized state structures, one similar to published models for other P2XR subtypes, and a second alternate conformation not previously observed. A loop adjacent to the orthosteric binding site between these two ATP-bound desensitized state structures undergoes significant conformational changes. These movements are supported by multireplicate, microsecond-scale molecular dynamics simulation studies and suggest a path by which ATP could enter or leave the orthosteric pocket. Together, our results provide structural insights into the P2X2R, facilitating structure-based drug development for this therapeutically important target.

Subtype-specific structural features of the hearing loss-associated human P2X2 receptor.,Westermann FG, Oken AC, Granith PKE, Marimuthu P, Muller CE, Mansoor SE Proc Natl Acad Sci U S A. 2025 Sep 16;122(37):e2417753122. doi: , 10.1073/pnas.2417753122. Epub 2025 Sep 12. PMID:40938707<ref>PMID:40938707</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ddv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mansoor SE]]
[[Category: Muller CE]]
[[Category: Oken AC]]
[[Category: Westermann FG]]