Structure of the human PKD1-PKD2 complex

被引：190

作者：

Su, Qiang ^{[1
]}

Hu, Feizhuo ^{[1
]}

Ge, Xiaofei ^{[1
]}

Lei, Jianlin ^{[2
]}

Yu, Shengqiang ^{[3
]}

Wang, Tingliang ^{[1
,4
]}

Zhou, Qiang ^{[1
]}

Mei, Chianglin ^{[3
]}

Shi, Yigong ^{[1
,4
]}

机构：

[1] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Tsinghua Peking Joint Ctr Life Sci, Sch Med,Sch Life Sci, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Minist Educ Key Lab Prot Sci, Technol Ctr Prot Sci, Sch Life Sci, Beijing 100084, Peoples R China

[3] Second Mil Med Univ, Changzheng Hosp, Dept Nephrol, Shanghai 200433, Peoples R China

[4] Westlake Univ, Inst Biol, Westlake Inst Adv Study, 18 Shilongshan Rd, Hangzhou 310064, Zhejiang, Peoples R China

来源：

SCIENCE | 2018年 / 361卷 / 6406期

基金：

中国国家自然科学基金;

关键词：

POLYCYSTIC KIDNEY-DISEASE; PKD2; MUTATIONS; PRIMARY CILIA; CHANNEL; PROTEIN; DOMAIN; GENE; IDENTIFICATION; EXPRESSION; INSIGHTS;

D O I：

10.1126/science.aat9819

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mutations in two genes, PKD1 and PKD2, 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.

引用

页码：992 / +

页数：8

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