ジャーナル: Nat Struct Mol Biol / 年: 2018 タイトル: Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. 著者: Zengqin Deng / Navid Paknejad / Grigory Maksaev / Monica Sala-Rabanal / Colin G Nichols / Richard K Hite / Peng Yuan / 要旨: The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present ...The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity. Structural comparisons with other TRP channels and distantly related voltage-gated cation channels reveal an unprecedented, unique packing interface between the voltage-sensor-like domain and the pore domain, suggesting distinct gating mechanisms. Moreover, our structure begins to provide mechanistic insights to the large set of pathogenic mutations, offering potential opportunities for drug development.
解像度: 6.5→20 Å / Cor.coef. Fo:Fc: 0.802 / Cor.coef. Fo:Fc free: 0.791 / SU B: 0.02 / SU ML: 0 / 交差検証法: THROUGHOUT / ESU R: 3.421 / ESU R Free: 3.501 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
Rfactor
反射数
%反射
Selection details
Rfree
0.37292
292
10.1 %
RANDOM
Rwork
0.36435
-
-
-
obs
0.36522
2589
95.4 %
-
溶媒の処理
イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK