Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function

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Standard

Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function. / Zhang, Liying; Simonsen, Charlotte; Zimova, Lucie; Wang, Kaituo; Moparthi, Lavanya; Gaudet, Rachelle; Ekoff, Maria; Nilsson, Gunnar; Hellmich, Ute A.; Vlachova, Viktorie; Gourdon, Pontus; Zygmunt, Peter M.

I: Nature Communications, Bind 13, Nr. 1, 7483, 2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Zhang, L, Simonsen, C, Zimova, L, Wang, K, Moparthi, L, Gaudet, R, Ekoff, M, Nilsson, G, Hellmich, UA, Vlachova, V, Gourdon, P & Zygmunt, PM 2022, 'Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function', Nature Communications, bind 13, nr. 1, 7483. https://doi.org/10.1038/s41467-022-35163-y

APA

Zhang, L., Simonsen, C., Zimova, L., Wang, K., Moparthi, L., Gaudet, R., Ekoff, M., Nilsson, G., Hellmich, U. A., Vlachova, V., Gourdon, P., & Zygmunt, P. M. (2022). Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function. Nature Communications, 13(1), [7483]. https://doi.org/10.1038/s41467-022-35163-y

Vancouver

Zhang L, Simonsen C, Zimova L, Wang K, Moparthi L, Gaudet R o.a. Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function. Nature Communications. 2022;13(1). 7483. https://doi.org/10.1038/s41467-022-35163-y

Author

Zhang, Liying ; Simonsen, Charlotte ; Zimova, Lucie ; Wang, Kaituo ; Moparthi, Lavanya ; Gaudet, Rachelle ; Ekoff, Maria ; Nilsson, Gunnar ; Hellmich, Ute A. ; Vlachova, Viktorie ; Gourdon, Pontus ; Zygmunt, Peter M. / Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function. I: Nature Communications. 2022 ; Bind 13, Nr. 1.

Bibtex

@article{9b37fccbd9ff484bbf1bc5c05cf5a5d3,
title = "Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function",
abstract = "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 Δ9-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.",
author = "Liying Zhang and Charlotte Simonsen and Lucie Zimova and Kaituo Wang and Lavanya Moparthi and Rachelle Gaudet and Maria Ekoff and Gunnar Nilsson and Hellmich, {Ute A.} and Viktorie Vlachova and Pontus Gourdon and Zygmunt, {Peter M.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-35163-y",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function

AU - Zhang, Liying

AU - Simonsen, Charlotte

AU - Zimova, Lucie

AU - Wang, Kaituo

AU - Moparthi, Lavanya

AU - Gaudet, Rachelle

AU - Ekoff, Maria

AU - Nilsson, Gunnar

AU - Hellmich, Ute A.

AU - Vlachova, Viktorie

AU - Gourdon, Pontus

AU - Zygmunt, Peter M.

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - 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 Δ9-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.

AB - 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 Δ9-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.

UR - http://www.scopus.com/inward/record.url?scp=85143312444&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-35163-y

DO - 10.1038/s41467-022-35163-y

M3 - Journal article

C2 - 36470868

AN - SCOPUS:85143312444

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 7483

ER -

ID: 329696259