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Updated: Jul 12, 2025

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Structure of human TRPM8 channel

Sergii Palchevskyi1,2, Mariusz Czarnocki-Cieciura1, Giulio Vistoli3

  • 1Laboratory of Protein Structure, International Institute of Molecular and Cell Biology in Warsaw, 02-109, Warsaw, Poland.

Communications Biology
|October 19, 2023
PubMed

Insights

Researchers visualized the human TRPM8 channel in its closed state using cryo-electron microscopy. This provides insights into TRPM8 channel structure and interactions, aiding anticancer drug development.

Area of Science:

  • Structural biology
  • Molecular biophysics
  • Ion channel research

Background:

  • Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective cation channel activated by various stimuli.
  • TRPM8 is a significant therapeutic target for anticancer drug development and managing pathological conditions.

Purpose of the Study:

  • To determine the high-resolution cryo-electron microscopy structure of the human TRPM8 channel in the closed state.
  • To elucidate the structural basis of TRPM8 channel function and interactions with ligands like icilin.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was employed to solve the structure of the human TRPM8 channel.
  • High-resolution structural analysis at 2.7 Å resolution.
  • Molecular modeling and comparative analysis of TRPM pore helices.

Main Results:

  • A 2.7 Å resolution cryo-EM structure of the human TRPM8 channel in the closed state was obtained.
  • The most complete model of the N-terminal pre-melastatin homology region was achieved.
  • Interactions with lipids and the modulator icilin were visualized and modeled.

Conclusions:

  • The determined structure provides a detailed view of the closed TRPM8 channel, including its N-terminal region and lipid interactions.
  • Analysis of pore helix conformations in TRPM structures allows classification into closed, desensitized, and open states.
  • This structural information is crucial for understanding TRPM8 channel gating and for designing targeted therapeutics.

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