Počet záznamů: 1
Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function
- 1.
SYSNO ASEP 0565702 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function Tvůrce(i) Zhang, L. (SE)
Simonsen, Ch. (SE)
Zímová, Lucie (FGU-C) RID, ORCID
Wang, K. (DK)
Moparthi, L. (SE)
Gaudet, R. (US)
Ekoff, M. (SE)
Nilsson, G. (SE)
Hellmich, U. A. (DE)
Vlachová, Viktorie (FGU-C) RID, ORCID, SAI
Gourdon, P. (SE)
Zygmunt, P. M. (SE)Číslo článku 7483 Zdroj.dok. Nature Communications. - : Nature Publishing Group
Roč. 13, č. 1 (2022)Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova TRPV cation channels ; cannabinoids ; cannabidiol ; ligand ; TRPV2 protein Obor OECD Neurosciences (including psychophysiology CEP GA22-13750S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000952021200020 EID SCOPUS 85143312444 DOI 10.1038/s41467-022-35163-y Anotace 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 delta9-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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2023 Elektronická adresa https://doi.org/10.1038/s41467-022-35163-y
Počet záznamů: 1