9B3Y
Rat TRPV2 E724A/D725A bound to probenecid
Summary for 9B3Y
| Entry DOI | 10.2210/pdb9b3y/pdb |
| EMDB information | 44160 |
| Descriptor | Transient receptor potential cation channel subfamily V member 2, 1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE, 4-(dipropylsulfamoyl)benzoic acid (3 entities in total) |
| Functional Keywords | trpv2, trp channel, probenecid, 2-apb, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 4 |
| Total formula weight | 350019.34 |
| Authors | Rocereta, J.A.,Pumroy, R.A.,Moiseenkova-Bell, V.Y. (deposition date: 2024-03-20, release date: 2025-02-26, Last modification date: 2025-07-02) |
| Primary citation | Rocereta, J.A.,Sturhahn, T.,Pumroy, R.A.,Fricke, T.C.,Herzog, C.,Leffler, A.,Moiseenkova-Bell, V. Structural insights into TRPV2 modulation by probenecid. Nat.Struct.Mol.Biol., 32:1019-1029, 2025 Cited by PubMed Abstract: The transient receptor potential vanilloid 2 (TRPV2) cation channel is a key player in cardiovascular physiology and pathophysiology. Probenecid (PBC), an FDA-approved uricosuric agent thought to activate TRPV2, has shown promise in enhancing cardiovascular function in both preclinical and clinical studies. Here our electrophysiological data reveal that PBC significantly potentiates rat TRPV2 to known stimuli, and cryo electron microscopy structures show that PBC directly interacts with rat TRPV2 in a previously unidentified intracellular binding pocket. PBC binding at a conserved TRPV2-specific histidine prevents the channel from taking on the inactivated carboxyl-terminal conformation. This effect extends to TRPV1 and TRPV3 channels when glutamine is substituted with histidine at the corresponding position, increasing their sensitivity to PBC. While PBC alone does not induce TRPV2 opening, its combination with 2-aminoethoxydiphenyl borate enables the channel to adopt an intermediate, potentiated state. Our results offer insights into potential therapeutic advancements for TRPV2 through this pocket. PubMed: 39972168DOI: 10.1038/s41594-025-01494-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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