6D1W

human PKD2 F604P mutant

Summary for 6D1W

• Entry DOI: 10.2210/pdb6d1w/pdb
• EMDB information: 7786
• Descriptor: Polycystin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: ion channel, trp channel, pkd2, pc2, trpp2, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 342639.84

Authors

Zheng, W.,Yang, X.,Bulkley, D.,Chen, X.Z.,Cao, E. (deposition date: 2018-04-12, release date: 2018-06-27, Last modification date: 2020-07-29)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.54 Å)