6U8A

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

6U8A の概要

• エントリーDOI: 10.2210/pdb6u8a/pdb
• 関連するPDBエントリー: 6U84 6U85 6U88
• EMDBエントリー: 20677 20678 20682 20686
• 分子名称: Transient receptor potential cation channel subfamily V member 2, cannabidiol (2 entities in total)
• 機能のキーワード: ion channel, trpv2, trp channel, cannabidiol, transport protein
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 348453.41

構造登録者

Pumroy, R.A.,Moiseenkova-Bell, V.Y. (登録日: 2019-09-04, 公開日: 2019-10-16, 最終更新日: 2024-03-20)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.4 Å)