9C48
Cryo-EM structure of the full-length human P2X4 receptor in the ATP-bound desensitized state
Summary for 9C48
| Entry DOI | 10.2210/pdb9c48/pdb |
| Related | 9BQH 9BQI |
| EMDB information | 44799 44800 45177 |
| Descriptor | P2X purinoceptor 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | membrane protein, ion channel, ligand-gated ion channel, p2x receptor, allosteric antagonist |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 138136.36 |
| Authors | Shi, H.,Ditter, I.A.,Oken, A.C.,Mansoor, S.E. (deposition date: 2024-06-03, release date: 2025-01-29) |
| Primary citation | Shi, H.,Ditter, I.A.,Oken, A.C.,Mansoor, S.E. Human P2X4 receptor gating is modulated by a stable cytoplasmic cap and a unique allosteric pocket. Sci Adv, 11:eadr3315-eadr3315, 2025 Cited by PubMed Abstract: 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. PubMed: 39823330DOI: 10.1126/sciadv.adr3315 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.4 Å) |
Structure validation
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