Structure of the human PKD1-PKD2 complex

• DOI: 10.1126/science.aat9819
• Publication Date: 2018-08-09T17:56:21Z
• Authors: Qiang Su; Feizhuo Hu; Xiaofei Ge; Jianlin Lei; Shengqiang Yu; Tingliang Wang; Qiang Zhou; Changlin Mei; Yigong Shi
• Keywords: Protein Folding; 0303 health sciences; 03 medical and health sciences; TRPP Cation Channels; Protein Domains; Multiprotein Complexes; Cryoelectron Microscopy; Mutation; Humans; Crystallography, X-Ray; Polycystic Kidney, Autosomal Dominant; 3. Good health

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