8jv5 | pdb_00008jv5

Cryo-EM structure of the zebrafish P2X4 receptor in complex with BX430

spinqualitylabelsall models 8jv5, resolution 3.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jv5 is a 3 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: Electron Microscopy, Resolution 3.23Å Ligands: NAG, P73 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] Publication Abstract from PubMed P2X receptors are ATP-activated cation channels, and the P2X4 subtype plays important roles in the immune system and the central nervous system, particularly in neuropathic pain. Therefore, P2X4 receptors are of increasing interest as potential drug targets. Here, we report the cryo-EM structures of the zebrafish P2X4 receptor in complex with two P2X4 subtype-specific antagonists, BX430 and BAY-1797. Both antagonists bind to the same allosteric site located at the subunit interface at the top of the extracellular domain. Structure-based mutational analysis by electrophysiology identified the important residues for the allosteric inhibition of both zebrafish and human P2X4 receptors. Structural comparison revealed the ligand-dependent structural rearrangement of the binding pocket to stabilize the binding of allosteric modulators, which in turn would prevent the structural changes of the extracellular domain associated with channel activation. Furthermore, comparison with the previously reported P2X structures of other subtypes provided mechanistic insights into subtype-specific allosteric inhibition. Structural insights into the allosteric inhibition of P2X4 receptors.,Shen C, Zhang Y, Cui W, Zhao Y, Sheng D, Teng X, Shao M, Ichikawa M, Wang J, Hattori M Nat Commun. 2023 Oct 13;14(1):6437. doi: 10.1038/s41467-023-42164-y. PMID:37833294 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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