6u8a
From Proteopedia
CBD-bound full-length rat TRPV2 in nanodiscs, state 1
Structural highlights
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 PubMedTransient 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 Cannabis sativa, 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. Molecular mechanism of TRPV2 channel modulation by cannabidiol.,Pumroy RA, Samanta A, Liu Y, Hughes TE, Zhao S, Yudin Y, Rohacs T, Han S, Moiseenkova-Bell VY Elife. 2019 Sep 30;8. pii: 48792. doi: 10.7554/eLife.48792. PMID:31566564[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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