Asset Details
Do you wish to reserve the book?
Structure of the human PKD1-PKD2 complex
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Structure of the human PKD1-PKD2 complex
Do you wish to request the book?
Structure of the human PKD1-PKD2 complex
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Structure of the human PKD1-PKD2 complex
2018
Overview
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 This structure provides a framework for further investigations into a complex involved in polycystic kidney disease. 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.
Publisher
The American Association for the Advancement of Science
Subject
/ Assembly
/ Cilia
/ Domains
/ Genes
/ Helices
/ Humans
/ Kidneys
/ Mapping
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - genetics
/ Multiprotein Complexes - ultrastructure
/ Mutation
/ Polycystic kidney disease 1 protein
/ Polycystic Kidney, Autosomal Dominant - genetics
/ Polycystic Kidney, Autosomal Dominant - metabolism
/ Proteins
/ Residues
/ Size exclusion chromatography
/ Stimuli
/ Toxins
/ Transient receptor potential proteins
/ TRPP Cation Channels - chemistry
/ TRPP Cation Channels - genetics
/ TRPP Cation Channels - metabolism
/ TRPP Cation Channels - ultrastructure
/ Voltage
/ α-Toxin
