9B73
Cryo-EM structure of the desensitised ATP-bound human P2X1 receptor
This is a non-PDB format compatible entry.
Summary for 9B73
| Entry DOI | 10.2210/pdb9b73/pdb |
| EMDB information | 44299 |
| Descriptor | P2X purinoceptor 1, ADENOSINE-5'-TRIPHOSPHATE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | ion channel, trimer, atp-bound, desensitised, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 138702.20 |
| Authors | Felix, M.B.,Alisa, G.,Hariprasad, V.,Jesse, I.M.,David, M.T. (deposition date: 2024-03-27, release date: 2024-10-09, Last modification date: 2024-10-30) |
| Primary citation | Bennetts, F.M.,Venugopal, H.,Glukhova, A.,Mobbs, J.I.,Ventura, S.,Thal, D.M. Structural insights into the human P2X1 receptor and ligand interactions. Nat Commun, 15:8418-8418, 2024 Cited by PubMed Abstract: The P2X1 receptor is a trimeric ligand-gated ion channel that plays an important role in urogenital and immune functions, offering the potential for new drug treatments. However, progress in this area has been hindered by limited structural information and a lack of well-characterised tool compounds. In this study, we employ cryogenic electron microscopy (cryo-EM) to elucidate the structures of the P2X1 receptor in an ATP-bound desensitised state and an NF449-bound closed state. NF449, a potent P2X1 receptor antagonist, engages the receptor distinctively, while ATP, the endogenous ligand, binds in a manner consistent with other P2X receptors. To explore the molecular basis of receptor inhibition, activation, and ligand interactions, key residues involved in ligand and metal ion binding were mutated. Radioligand binding assays with [H]-α,β-methylene ATP and intracellular calcium ion influx assays were used to evaluate the effects of these mutations. These experiments validate key ligand-receptor interactions and identify conserved and non-conserved residues critical for ligand binding or receptor modulation. This research expands our understanding of the P2X1 receptor structure at a molecular level and opens new avenues for in silico drug design targeting the P2X1 receptor. PubMed: 39341830DOI: 10.1038/s41467-024-52776-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (1.96 Å) |
Structure validation
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