PUBLICATION
Electron cryo-microscopy structure of the canonical TRPC4 ion channel
- Authors
- Vinayagam, D., Mager, T., Apelbaum, A., Bothe, A., Merino, F., Hofnagel, O., Gatsogiannis, C., Raunser, S.
- ID
- ZDB-PUB-180503-4
- Date
- 2018
- Source
- eLIFE 7: (Journal)
- Registered Authors
- Keywords
- molecular biophysics, structural biology, zebrafish
- MeSH Terms
-
- Animals
- Cryoelectron Microscopy
- Models, Molecular
- Molecular Conformation
- Protein Domains
- TRPC Cation Channels/chemistry
- TRPC Cation Channels/ultrastructure*
- Zebrafish
- PubMed
- 29717981 Full text @ Elife
Citation
Vinayagam, D., Mager, T., Apelbaum, A., Bothe, A., Merino, F., Hofnagel, O., Gatsogiannis, C., Raunser, S. (2018) Electron cryo-microscopy structure of the canonical TRPC4 ion channel. eLIFE. 7.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping