+検索条件
-Structure paper
タイトル | Structure and gating mechanism of the transient receptor potential channel TRPV3. |
---|---|
ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 25, Issue 9, Page 805-813, Year 2018 |
掲載日 | 2018年8月20日 |
著者 | Appu K Singh / Luke L McGoldrick / Alexander I Sobolevsky / |
PubMed 要旨 | Transient receptor potential vanilloid subfamily member 3 (TRPV3) channel plays a crucial role in skin physiology and pathophysiology. Mutations in TRPV3 are associated with various skin diseases, ...Transient receptor potential vanilloid subfamily member 3 (TRPV3) channel plays a crucial role in skin physiology and pathophysiology. Mutations in TRPV3 are associated with various skin diseases, including Olmsted syndrome, atopic dermatitis, and rosacea. Here we present the cryo-electron microscopy structures of full-length mouse TRPV3 in the closed apo and agonist-bound open states. The agonist binds three allosteric sites distal to the pore. Channel opening is accompanied by conformational changes in both the outer pore and the intracellular gate. The gate is formed by the pore-lining S6 helices that undergo local α-to-π helical transitions, elongate, rotate, and splay apart in the open state. In the closed state, the shorter S6 segments are entirely α-helical, expose their nonpolar surfaces to the pore, and hydrophobically seal the ion permeation pathway. These findings further illuminate TRP channel activation and can aid in the design of drugs for the treatment of inflammatory skin conditions, itch, and pain. |
リンク | Nat Struct Mol Biol / PubMed:30127359 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.0 - 6.5 Å |
構造データ | EMDB-8920, PDB-6dvy: EMDB-8921, PDB-6dvz: EMDB-8925: |
化合物 | ChemComp-FZ4: |
由来 |
|
キーワード | MEMBRANE PROTEIN / TRPV3 / TRP channels / Calcium channels |