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- Title
Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.
- Authors
Wang Zheng; Xiaoyong Yang; Ruikun Hu; Ruiqi Cai; Hofmann, Laura; Zhifei Wang; Qiaolin Hu; Xiong Liu; Bulkley, David; Yong Yu; Jingfeng Tang; Flockerzi, Veit; Ying Cao; Erhu Cao; Xing-Zhen Chen
- Abstract
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.
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04586-x