Related Experiment Video

Updated: Feb 11, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

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Structure of the receptor-activated human TRPC6 and TRPC3 ion channels

Qinglin Tang1, Wenjun Guo1, Li Zheng2

  • 1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, 100871, Beijing, China.

Cell Research
|April 28, 2018
PubMed

Insights

Researchers reveal the molecular architecture of TRPC6 and TRPC3 channels using cryo-EM. Structures show how a novel inhibitor, BTDM, blocks TRPC6 channel activity, offering insights into channel function and disease.

Area of Science:

  • Structural Biology
  • Molecular Physiology
  • Biophysics

Background:

  • Canonical transient receptor potential (TRPC) channels, including TRPC6 and TRPC3, are nonselective cation channels activated by diacylglycerol.
  • These channels play critical roles in numerous physiological processes and are linked to human genetic disorders.

Purpose of the Study:

  • To determine the high-resolution structures of human TRPC6 and TRPC3 channels.
  • To elucidate the mechanism of inhibition by a novel high-affinity inhibitor, BTDM, for TRPC6.

Main Methods:

  • Single-particle cryo-electron microscopy (cryo-EM) was employed to solve the structures.
  • High-resolution structural determination of human TRPC6 homotetramer (3.8 Å) and TRPC3 (4.4 Å).

Main Results:

  • The structures reveal a two-layer architecture comprising a cytosolic bell-shaped layer and a transmembrane layer.
  • Extensive inter-subunit interactions stabilize the tetrameric assembly of TRPC channels.
  • The inhibitor BTDM binds between the S5-S6 pore domain and voltage sensor-like domain, effectively blocking channel opening.

Conclusions:

  • The determined structures provide unprecedented molecular insights into the architecture of TRPC channels.
  • These findings offer a structural foundation for understanding TRPC channel mechanisms and for the rational design of therapeutic agents.

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