Structure of the human PKD1-PKD2 complex

作者：Qiang Su, Feizhuo Hu, Xiaofei Ge, Jianlin Lei, Shengqiang Yu, Tingliang Wang, Qiang Zhou, Changlin Mei, Yigong Shi · 发表于：Science · 年份：2018 · DOI：10.1126/science.aat9819 · 被引用次数：288 · 研究领域：Genetic and Kidney Cyst Diseases、Genetic Syndromes and Imprinting、Renal and related cancers

, 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.