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-Structure paper
| タイトル | Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 9, Issue 1, Page 2302, Year 2018 |
| 掲載日 | 2018年6月13日 |
著者 | Wang Zheng / Xiaoyong Yang / Ruikun Hu / Ruiqi Cai / Laura Hofmann / Zhifei Wang / Qiaolin Hu / Xiong Liu / David Bulkley / Yong Yu / Jingfeng Tang / Veit Flockerzi / Ying Cao / Erhu Cao / Xing-Zhen Chen / ![]() |
| PubMed 要旨 | PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to ...PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2. We find that a PKD2 gain-of-function gate mutant effectively rescues PKD2 knockdown-induced phenotypes in embryonic zebrafish. The structure of a PKD2 activating mutant F604P by cryo-electron microscopy reveals a π- to α-helix transition within the pore-lining helix S6 that leads to repositioning of the gate residue and channel activation. Overall the results identify hydrophobic gates and a gating mechanism of PKD2 and PKD2L1. |
リンク | Nat Commun / PubMed:29899465 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.54 Å |
| 構造データ | |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | TRANSPORT PROTEIN / Ion Channel / TRP channel / PKD2 / PC2 / TRPP2 |
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homo sapiens (ヒト)
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