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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yin, Y; Wu, M; Zubcevic, L; Borschel, WF; Lander, GC; Lee, S-Y

Published Date

  • January 12, 2018

Published In

Volume / Issue

  • 359 / 6372

Start / End Page

  • 237 - 241

PubMed ID

  • 29217583

Pubmed Central ID

  • PMC5810135

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aan4325


  • eng

Conference Location

  • United States