6D1W

human PKD2 F604P mutant

6D1W の概要

• エントリーDOI: 10.2210/pdb6d1w/pdb
• EMDBエントリー: 7786
• 分子名称: Polycystin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: ion channel, trp channel, pkd2, pc2, trpp2, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 342639.84

構造登録者

Zheng, W.,Yang, X.,Bulkley, D.,Chen, X.Z.,Cao, E. (登録日: 2018-04-12, 公開日: 2018-06-27, 最終更新日: 2025-05-21)

主引用文献

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, X.Z.
Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.
Nat Commun, 9:2302-2302, 2018

PubMed 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.

PubMed: 29899465
DOI: 10.1038/s41467-018-04586-x

実験手法

ELECTRON MICROSCOPY (3.54 Å)