9bqi
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of BAY-1797 bound to the full-length human P2X4 receptor in the closed state== | |
| + | <StructureSection load='9bqi' size='340' side='right'caption='[[9bqi]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9bqi]] 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=9BQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BQI 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]] 2.55Å</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=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6E:~{N}-[4-(3-chloranylphenoxy)-3-sulfamoyl-phenyl]-2-phenyl-ethanamide'>P6E</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=9bqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bqi OCA], [https://pdbe.org/9bqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bqi RCSB], [https://www.ebi.ac.uk/pdbsum/9bqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bqi ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/P2RX4_HUMAN P2RX4_HUMAN] ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium (PubMed:9016352). CTP, but not GTP or UTP, functions as a weak affinity agonist for P2RX4 (By similarity). Activated by extracellularly released ATP, it plays multiple role in immunity and central nervous system physiology (PubMed:35165166). Plays a key role in initial steps of T-cell activation and Ca(2+) microdomain formation (By similarity). Participates also in basal T-cell activity without TCR/CD3 stimulation (By similarity). Promotes the differentiation and activation of Th17 cells via expression of retinoic acid-related orphan receptor C/RORC (PubMed:35165166). Upon activation, drives microglia motility via the PI3K/Akt pathway (By similarity). Could also function as an ATP-gated cation channel of lysosomal membranes (By similarity).[UniProtKB:P51577][UniProtKB:Q9JJX6]<ref>PMID:35165166</ref> <ref>PMID:9016352</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | P2X receptors (P2XRs) are adenosine 5'-triphosphate (ATP)-gated ion channels comprising homomeric and heteromeric trimers of seven subtypes (P2X1-P2X7) that confer different rates of desensitization. The helical recoil model of P2XR desensitization proposes stability of the cytoplasmic cap sets the rate of desensitization, but timing of its formation is unclear for slow-desensitizing P2XRs. We report cryo-electron microscopy structures of full-length wild-type human P2X4 receptor in apo closed, antagonist-bound inhibited, and ATP-bound desensitized states. Because the apo closed and antagonist-bound inhibited state structures of this slow-desensitizing P2XR include an intact cytoplasmic cap while the ATP-bound desensitized state structure does not, the cytoplasmic cap is formed before agonist binding. Furthermore, structural and functional data suggest the cytoplasmic cap is stabilized by lipids to modulate desensitization, and P2X4 is modified by glycosylation and palmitoylation. Last, our antagonist-bound inhibited state structure reveals features specific to the allosteric ligand-binding pocket in human receptors that facilitates development of small-molecule modulators. | ||
| - | + | Human P2X4 receptor gating is modulated by a stable cytoplasmic cap and a unique allosteric pocket.,Shi H, Ditter IA, Oken AC, Mansoor SE Sci Adv. 2025 Jan 17;11(3):eadr3315. doi: 10.1126/sciadv.adr3315. Epub 2025 Jan , 17. PMID:39823330<ref>PMID:39823330</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9bqi" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ditter IA]] | ||
| + | [[Category: Mansoor SE]] | ||
| + | [[Category: Oken AC]] | ||
| + | [[Category: Shi H]] | ||
Current revision
Cryo-EM structure of BAY-1797 bound to the full-length human P2X4 receptor in the closed state
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