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Updated: Jan 21, 2026

Routine Collection of High-Resolution cryo-EM Datasets Using 200 KV Transmission Electron Microscope
Published on: March 16, 2022
Cryo-EM structure of TRPC5 at 2.8-Å resolution reveals unique and conserved structural elements essential for channel
Jingjing Duan1,2,3, Jian Li4,5, Gui-Lan Chen6,7
1Human Aging Research Institute (HARI), School of Life Sciences, Nanchang University, Nanchang, Jiangxi 330031, China.
Abstract:
The transient receptor potential canonical subfamily member 5 (TRPC5), one of seven mammalian TRPC members, is a nonselective calcium-permeant cation channel. TRPC5 is of considerable interest as a drug target in the treatment of progressive kidney disease, depression, and anxiety. Here, we present the 2.8-Å resolution cryo-electron microscopy (cryo-EM) structure of the mouse TRPC5 (mTRPC5) homotetramer. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. The disulfide bond at the extracellular side of the pore and a preceding small loop are essential elements for its proper function. This high-resolution structure of mTRPC5, combined with electrophysiology and mutagenesis, provides insight into the lipid modulation and gating mechanisms of the TRPC family of ion channels.
Insights
We determined the high-resolution cryo-electron microscopy structure of the mouse TRPC5 (transient receptor potential canonical subfamily member 5) channel. This reveals key structural differences and provides insights into TRPC5 ion channel function and gating.
Area of Science:
- Structural biology
- Ion channel biophysics
- Molecular pharmacology
Background:
- Transient receptor potential canonical subfamily member 5 (TRPC5) is a calcium-permeant cation channel.
- TRPC5 is a significant drug target for progressive kidney disease, depression, and anxiety.
- Understanding TRPC5 structure is crucial for developing targeted therapeutics.
Purpose of the Study:
- To determine the high-resolution structure of the mouse TRPC5 (mTRPC5) homotetramer.
- To identify structural differences between TRPC5 and other TRP channels.
- To elucidate the mechanisms of lipid modulation and gating in TRPC channels.
Main Methods:
- Cryo-electron microscopy (cryo-EM) at 2.8-Å resolution
- Electrophysiology
- Site-directed mutagenesis
Main Results:
- The 2.8-Å resolution cryo-EM structure of the mTRPC5 homotetramer was determined.
- Structural comparisons revealed distinct extracellular pore domain features and S3 helix lengths in TRPC5.
- A disulfide bond and adjacent loop on the extracellular pore are critical for mTRPC5 function.
Conclusions:
- The high-resolution mTRPC5 structure offers critical insights into ion channel architecture.
- Structural findings illuminate TRPC5's role in lipid modulation and gating mechanisms.
- This work provides a foundation for TRPC5-targeted drug development.
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