Gene

Kidney

Cell biology

Engineering

Ecology

Biology

Receptor

Mutation

Folding (DSP implementation)

Biochemistry

Computational biology

PKD1

Genetics

Membrane

Helix (gastropod)

Internal medicine

Polycystic kidney disease

Medicine

Chemistry

Transmembrane domain

Biophysics

Transmembrane protein

Disease

Snail

Ion channel

Autosomal dominant polycystic kidney disease

Electrical engineering

Science

A complex implicated in kidney health Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease that can lead to kidney failure. Mutations in the proteins PKD1 and PKD2 are linked to the disease, but the function of these proteins remains unclear, both in physiology and disease. PKD1 has been implicated in the sensing of chemical and mechanical force stimuli, and PKD2 is proposed to be a calcium ion channel. Su et al. show that the transmembrane regions form a PKD1-PKD2 complex assembled in a 1:3 ratio. Their high-resolution cryo–electron microscopy structure confirms that the complex adopts transient receptor potential channel architecture, with some distinctive features. Mapping disease-causing mutations onto the structure suggests that pathogenesis may come from incorrect folding or trafficking of the complex rather than from disruption of channel activity. Science , this issue p. eaat9819

Structure of the human PKD1-PKD2 complex