Structure of the human PKD1-PKD2 complex.
basic_science · Level V
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- Record sourced from PubMed, PMID 30093605.
- Also identified by DOI 10.1126/science.aat9819.
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Abstract
Mutations in two genes, <i>PKD1</i> and <i>PKD2</i>, 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.
Medical subject headings
- Multiprotein Complexes
- Polycystic Kidney, Autosomal Dominant
- TRPP Cation Channels