Structure of the human PKD1-PKD2 complex

Science. 2018 Sep 7;361(6406):eaat9819. doi: 10.1126/science.aat9819. Epub 2018 Aug 9.


Mutations in two genes, PKD1 and PKD2, account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo-electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five-transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Humans
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / ultrastructure
  • Mutation
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Protein Domains
  • Protein Folding
  • TRPP Cation Channels / chemistry*
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / metabolism
  • TRPP Cation Channels / ultrastructure


  • Multiprotein Complexes
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein