Electron cryo-microscopy structure of the canonical TRPC4 ion channel

Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2018-05, Vol.7
Main Authors: Vinayagam, Deivanayagabarathy, Mager, Thomas, Apelbaum, Amir, Bothe, Arne, Merino, Felipe, Hofnagel, Oliver, Gatsogiannis, Christos, Raunser, Stefan
Format: Article
Language:English
Subjects:
Animals
Calcium signalling
Cancer
cation channel
cryo-EM
Cryoelectron Microscopy
Danio rerio
Experiments
Kidney cancer
Lipids
Models, Molecular
Molecular Conformation
Protein Domains
Proteins
Receptor channels
SPHIRE
Structural Biology and Molecular Biophysics
structure
transient receptor channel
Transient receptor potential proteins
TRPC
TRPC Cation Channels - chemistry
TRPC Cation Channels - ultrastructure
Zebrafish
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.36615