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-Structure paper
タイトル | Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 25, Issue 3, Page 252-260, Year 2018 |
掲載日 | 2018年2月26日 |
著者 | Zengqin Deng / Navid Paknejad / Grigory Maksaev / Monica Sala-Rabanal / Colin G Nichols / Richard K Hite / Peng Yuan / |
PubMed 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. |
リンク | Nat Struct Mol Biol / PubMed:29483651 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.8 - 6.5 Å |
構造データ | PDB-6c8f: PDB-6c8g: PDB-6c8h: |
化合物 | ChemComp-CS: ChemComp-BA: ChemComp-GD: |
由来 |
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キーワード | METAL TRANSPORT / Ion Channel / TRP channel / TRANSPORT PROTEIN / ion channal |