National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM103899
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM129357
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01NS055159
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM093290
United States
Citation
Journal: Elife / Year: 2019 Title: Molecular mechanism of TRPV2 channel modulation by cannabidiol. Authors: Ruth A Pumroy / Amrita Samanta / Yuhang Liu / Taylor Et Hughes / Siyuan Zhao / Yevgen Yudin / Tibor Rohacs / Seungil Han / Vera Y Moiseenkova-Bell / Abstract: Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ...Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of , is an activator of TRPV2 and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length rat TRPV2 channel in apo and CBD-bound states in nanodiscs by cryo-electron microscopy. We show that CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. CBD-bound TRPV2 structures revealed that the S4-S5 linker plays a critical role in channel gating upon CBD binding. Additionally, nanodiscs permitted us to visualize two distinct TRPV2 apo states in a lipid environment. Together these results provide a foundation to further understand TRPV channel gating, their divergent physiological functions, and to accelerate structure-based drug design.
History
Deposition
Sep 4, 2019
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Header (metadata) release
Oct 2, 2019
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Map release
Oct 16, 2019
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Update
Mar 20, 2024
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Current status
Mar 20, 2024
Processing site: RCSB / Status: Released
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