Molecular mechanism of TRPV2 channel modulation by cannabidiol

Ruth A. Pumroy, Amrita Samanta, Yuhang Liu, Taylor E.T. Hughes, Siyuan Zhao, Yevgen Yudin, Tibor Rohacs, Seungil Han, Vera Y. Moiseenkova-Bell

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Transient receptor potential vanilloid (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is an activator of TRPV and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length rat TRPV channel in apo and CBD-bound states in nanodiscs by cryoelectron microscopy. We show that CBD interacts with TRPV through a hydrophobic pocket located between S and S helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. CBD-bound TRPV 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 TRPV 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.

Original languageEnglish (US)
Article numbere48792
StatePublished - Sep 2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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