Electron cryo-microscopy structure of the canonical TRPC4 ion channel

Abstract
Data availability
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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.

The following data sets were generated

1. Vinayagam D
2. Mager T
3. Apelbaum A
4. Bothe A
5. Merino F
6. Hofnagel O
7. Gatsogiannis G
8. Raunser S
(2018) Electron cryo-microscopy structure of the canonical TRPC4 ion channel
Publicly available at the RCSB Protein Data Bank (accession number ID 6G1K).

https://www.rcsb.org/structure/6G1K
1. Vinayagam D
2. Mager T
3. Apelbaum A
4. Bothe A
5. Merino F
6. Hofnagel O
7. Gatsogiannis G
8. Raunser S
(2018) Electron cryo-microscopy structure of the canonical TRPC4 ion channel
Publicly available at the EMDataBank (accession no. EMD-4339).

http://emsearch.rutgers.edu/atlas/4339_summary.html

Article and author information

Author details

Deivanayagabarathy Vinayagam

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
Thomas Mager

Department of Biophysical Chemistry, Max Planck Institute of Biophysics, Frankfurt am Main, Germany

Competing interests
The authors declare that no competing interests exist.
Amir Apelbaum

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
Arne Bothe

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
Felipe Merino

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4166-8747
Oliver Hofnagel

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
Christos Gatsogiannis

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
Stefan Raunser

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

For correspondence
stefan.raunser@mpi-dortmund.mpg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9373-3016

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.

Copyright

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.