Structure of the cold- and menthol-sensing ion channel TRPM8

Science. 2018 Jan 12;359(6372):237-241. doi: 10.1126/science.aan4325. Epub 2017 Dec 7.


Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer. The structure suggests that the menthol-binding site is located within the voltage-sensor-like domain and thus provides a structural glimpse of the design principle of the molecular transducer for cold and menthol sensation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Avian Proteins / chemistry*
  • Avian Proteins / metabolism
  • Avian Proteins / ultrastructure
  • Binding Sites
  • Cold Temperature
  • Cryoelectron Microscopy
  • Image Processing, Computer-Assisted
  • Menthol / metabolism*
  • Models, Molecular
  • Passeriformes / metabolism*
  • Protein Domains
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Subunits
  • TRPM Cation Channels / chemistry*
  • TRPM Cation Channels / metabolism
  • TRPM Cation Channels / ultrastructure


  • Avian Proteins
  • Protein Subunits
  • TRPM Cation Channels
  • Menthol