8TRJ
Cryo-EM structure of the rat P2X7 receptor in complex with the high-affinity agonist BzATP
This is a non-PDB format compatible entry.
Summary for 8TRJ
| Entry DOI | 10.2210/pdb8trj/pdb |
| Related | 8TR5 8TR6 8TR7 8TR8 8TRA 8TRB 8TRK |
| EMDB information | 41570 41571 41572 41573 41575 41576 41581 41582 |
| Descriptor | P2X purinoceptor 7, 3'-O-(4-benzoylbenzoyl)adenosine 5'-(tetrahydrogen triphosphate), GUANOSINE-5'-DIPHOSPHATE, ... (7 entities in total) |
| Functional Keywords | membrane protein, ion channel, ligand-gate ion channel, p2x receptor, allosteric antagonist, high-affinity agonist |
| Biological source | Rattus More |
| Total number of polymer chains | 3 |
| Total formula weight | 215122.85 |
| Authors | Oken, A.C.,Lisi, N.E.,Krishnamurthy, I.,McCarthy, A.E.,Godsey, M.H.,Glasfeld, A.,Mansoor, S.E. (deposition date: 2023-08-09, release date: 2024-08-14, Last modification date: 2025-05-14) |
| Primary citation | Oken, A.C.,Lisi, N.E.,Krishnamurthy, I.,McCarthy, A.E.,Godsey, M.H.,Glasfeld, A.,Mansoor, S.E. High-affinity agonism at the P2X 7 receptor is mediated by three residues outside the orthosteric pocket. Nat Commun, 15:6662-6662, 2024 Cited by PubMed Abstract: P2X receptors are trimeric ATP-gated ion channels that activate diverse signaling cascades. Due to its role in apoptotic pathways, selective activation of P2X is a potential experimental tool and therapeutic approach in cancer biology. However, mechanisms of high-affinity P2X activation have not been defined. We report high-resolution cryo-EM structures of wild-type rat P2X bound to the high-affinity agonist BzATP as well as significantly improved apo receptor structures in the presence and absence of sodium. Apo structures define molecular details of pore architecture and reveal how a partially hydrated Na ion interacts with the conductance pathway in the closed state. Structural, electrophysiological, and direct binding data of BzATP reveal that three residues just outside the orthosteric ATP-binding site are responsible for its high-affinity agonism. This work provides insights into high-affinity agonism for any P2X receptor and lays the groundwork for development of subtype-specific agonists applicable to cancer therapeutics. PubMed: 39107314DOI: 10.1038/s41467-024-50771-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.78 Å) |
Structure validation
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