Research Article

Structure of the human PKD1/PKD2 complex

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Science  09 Aug 2018:
eaat9819
DOI: 10.1126/science.aat9819

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Abstract

Mutations in two genes, pkd1 and pkd2, account for most cases of autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders. Here we report the 3.6 Å cryo-EM 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 non-canonical, TRP channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular 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 VGIC, a 5-TM 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.

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