5T4D : Cryo-EM structure of Polycystic Kidney Disease protein 2 (PKD2), residues 198-703

  • Peter S. Shen (Contributor)
  • Xiaoyong Yang (Contributor)
  • Paul Gregory DeCaen (Contributor)
  • Xiaowen Liu (Contributor)
  • David Bulkley (Contributor)
  • David E. Clapham (Contributor)
  • Erhu Cao (Contributor)

Dataset

Description

Experimental Technique/Method:ELECTRON MICROSCOPY
Resolution:3.0
Classification:METAL TRANSPORT
Release Date:2016-11-02
Deposition Date:2016-08-29
Revision Date:2016-11-09#2016-11-30#2017-11-08
Molecular Weight:240371.08
Macromolecule Type:Protein
Residue Count:2040
Atom Site Count:14876
DOI:10.2210/pdb5t4d/pdb

Abstract:
The Polycystic Kidney Disease 2 (Pkd2) gene is mutated in autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic disorders. Here, we present the cryo-EM structure of PKD2 in lipid bilayers at 3.0 Å resolution, which establishes PKD2 as a homotetrameric ion channel and provides insight into potential mechanisms for its activation. The PKD2 voltage-sensor domain retains two of four gating charges commonly found in those of voltage-gated ion channels. The PKD2 ion permeation pathway is constricted at the selectivity filter and near the cytoplasmic end of S6, suggesting that two gates regulate ion conduction. The extracellular domain of PKD2, a hotspot for ADPKD pathogenic mutations, contributes to channel assembly and strategically interacts with the transmembrane core, likely serving as a physical substrate for extracellular stimuli to allosterically gate the channel. Finally, our structure establishes the molecular basis for the majority of pathogenic mutations in Pkd2-related ADPKD.
Date made available2016
PublisherRCSB-PDB

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