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

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.

SUBMITTER: Yin Y

PROVIDER: S-EPMC5810135 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Yin Ying Y Wu Mengyu M Zubcevic Lejla L Borschel William F WF Lander Gabriel C GC Lee Seok-Yong SY

Science (New York, N.Y.) 20171207 6372

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 kno ...[more]

PMID: 29217583

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