7zjh

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TRPV2-C16+Pro-2

Structural highlights

7zjh is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.39Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRPV2_RAT Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by growth factors, like IGF1, PDGF and morphogenetic neuropeptide/head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH (By similarity).[1] [2]

Publication Abstract from PubMed

TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore how TRPV2 activity is modulated by the phytocannabinoid Delta(9)-tetrahydrocannabiorcol (C16) and by probenecid. C16 and probenecid act in concert to stimulate TRPV2 responses including histamine release from rat and human mast cells. Each ligand causes distinct conformational changes in TRPV2 as revealed by cryo-EM. Although the binding for probenecid remains elusive, C16 associates within the vanilloid pocket. As such, the C16 binding location is distinct from that of cannabidiol, partially overlapping with the binding site of the TRPV2 inhibitor piperlongumine. Taken together, we discover a new cannabinoid binding site in TRPV2 that is under the influence of allosteric control by probenecid. This molecular insight into ligand modulation enhances our understanding of TRPV2 in normal and pathophysiology.

Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function.,Zhang L, Simonsen C, Zimova L, Wang K, Moparthi L, Gaudet R, Ekoff M, Nilsson G, Hellmich UA, Vlachova V, Gourdon P, Zygmunt PM Nat Commun. 2022 Dec 5;13(1):7483. doi: 10.1038/s41467-022-35163-y. PMID:36470868[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature. 1999 Apr 1;398(6726):436-41. PMID:10201375 doi:http://dx.doi.org/10.1038/18906
  2. ↑ Stokes AJ, Shimoda LM, Koblan-Huberson M, Adra CN, Turner H. A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. J Exp Med. 2004 Jul 19;200(2):137-47. Epub 2004 Jul 12. PMID:15249591 doi:http://dx.doi.org/10.1084/jem.20032082
  3. ↑ Zhang L, Simonsen C, Zimova L, Wang K, Moparthi L, Gaudet R, Ekoff M, Nilsson G, Hellmich UA, Vlachova V, Gourdon P, Zygmunt PM. Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function. Nat Commun. 2022 Dec 5;13(1):7483. doi: 10.1038/s41467-022-35163-y. PMID:36470868 doi:http://dx.doi.org/10.1038/s41467-022-35163-y

Contents


PDB ID 7zjh

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