9BPC
Cryo-EM structure of P2X3 receptor in complex with camlipixant
This is a non-PDB format compatible entry.
Summary for 9BPC
| Entry DOI | 10.2210/pdb9bpc/pdb |
| Related | 5svj 5svk |
| EMDB information | 44771 |
| Descriptor | P2X purinoceptor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, Camlipixant, ... (4 entities in total) |
| Functional Keywords | p2x3, camlipixant, cryo-em, ion channel, receptor, membrane protein |
| Biological source | Canis lupus (gray wolf) |
| Total number of polymer chains | 3 |
| Total formula weight | 124744.76 |
| Authors | |
| Primary citation | Thach, T.,Dhanabalan, K.,Nandekar, P.P.,Stauffer, S.,Heisler, I.,Alvarado, S.,Snyder, J.,Subramanian, R. Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist. J.Biol.Chem., 301:108109-108109, 2025 Cited by PubMed Abstract: ATP-activated P2X3 receptors play a pivotal role in chronic cough, affecting more than 10% of the population. Despite the challenges posed by the highly conserved structure of P2X receptors, efforts to develop selective drugs targeting P2X3 have led to the development of camlipixant, a potent, selective P2X3 antagonist. However, the mechanisms of receptor desensitization, ion permeation, and structural basis of camlipixant binding to P2X3 remain unclear. Here, we report a cryo-EM structure of camlipixant-bound P2X3, revealing a previously undiscovered selective drug-binding site in the receptor. Our findings also demonstrate that conformational changes in the upper body domain, including the turret and camlipixant-binding pocket, play a critical role: turret opening facilitates P2X3 channel closure to a radius of 0.7 Å, hindering cation transfer, whereas turret closure leads to channel opening. Structural and functional studies combined with molecular dynamics simulations provide a comprehensive understanding of camlipixant's selective inhibition of P2X3, offering a foundation for future drug development targeting this receptor. PubMed: 39706278DOI: 10.1016/j.jbc.2024.108109 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.44 Å) |
Structure validation
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