EMD-7786
human PKD2 F604P mutant
EMD-7786
Single-particle3.54 Å
Deposition: 12/04/2018Map released: 27/06/2018
Last modified: 13/11/2024
Sample Organism:
Homo sapiens
Sample: PKD2
Fitted models: 6d1w (Avg. Q-score: 0.405)
Deposition Authors: Zheng W, Yang X
Sample: PKD2
Fitted models: 6d1w (Avg. Q-score: 0.405)
Deposition Authors: Zheng W, Yang X
Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.
Zheng W,
Yang X,
Hu R,
Cai R,
Hofmann L,
Wang Z 
,
Hu Q,
Liu X ,
Bulkey D ,
Yu Y ,
Tang J ,
Flockerzi V ,
Cao Y,
Cao E,
Chen XZ
(2018) Nat Commun , 9 , 2302 - 2302
,
Hu Q,
Liu X ,
Bulkey D ,
Yu Y ,
Tang J ,
Flockerzi V ,
Cao Y,
Cao E,
Chen XZ
(2018) Nat Commun , 9 , 2302 - 2302
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.
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.