6U8A

CBD-bound full-length rat TRPV2 in nanodiscs, state 1

Summary for 6U8A

• Entry DOI: 10.2210/pdb6u8a/pdb
• Related: 6U84 6U85 6U88
• EMDB information: 20677 20678 20682 20686
• Descriptor: Transient receptor potential cation channel subfamily V member 2, cannabidiol (2 entities in total)
• Functional Keywords: ion channel, trpv2, trp channel, cannabidiol, transport protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 348453.41

Authors

Pumroy, R.A.,Moiseenkova-Bell, V.Y. (deposition date: 2019-09-04, release date: 2019-10-16, Last modification date: 2024-03-20)

Primary citation

Pumroy, R.A.,Samanta, A.,Liu, Y.,Hughes, T.E.,Zhao, S.,Yudin, Y.,Rohacs, T.,Han, S.,Moiseenkova-Bell, V.Y.
Molecular mechanism of TRPV2 channel modulation by cannabidiol.
Elife, 8:-, 2019

PubMed 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 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.

PubMed: 31566564
DOI: 10.7554/eLife.48792

Experimental method

ELECTRON MICROSCOPY (3.4 Å)