Electron cryo-microscopy structure of the canonical TRPC4 ion channel
- Max Planck Institute of Molecular Physiology, Germany
- Max Planck Institute of Biophysics, Germany
Abstract
Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ 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.
Data availability
The atomic coordinates and cryo-EM maps for TRPC4DR are available at the Protein Data Bank (PDB)/Electron Microscopy Data Bank (EMDB) databases. The accession numbers are 6G1K/EMD-4339. The raw data sets generated in the current study (motion corrected and dose weighted mrc files and box files; 215 GB) are available from the corresponding author upon request.
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Electron cryo-microscopy structure of the canonical TRPC4 ion channelPublicly available at the RCSB Protein Data Bank (accession number ID 6G1K).
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Electron cryo-microscopy structure of the canonical TRPC4 ion channelPublicly available at the EMDataBank (accession no. EMD-4339).
Article and author information
Author details
Funding
Max-Planck-Gesellschaft (Open-access funding)
- Stefan Raunser
European Commission (615984)
- Stefan Raunser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kenton J Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
Version history
- Received: March 12, 2018
- Accepted: April 30, 2018
- Accepted Manuscript published: May 2, 2018 (version 1)
- Version of Record published: May 14, 2018 (version 2)
Copyright
© 2018, Vinayagam et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Electron cryo-microscopy structure of the canonical TRPC4 ion channel
eLife 7:e36615.
https://doi.org/10.7554/eLife.36615
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