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

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

Author information

1
Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
2
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

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.

PMID:
29217583
PMCID:
PMC5810135
[Available on 2018-07-12]
DOI:
10.1126/science.aan4325
[Indexed for MEDLINE]

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