GSTDTAP  > 地球科学
DOI10.1126/science.aav9334
Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel
Yin, Ying1; Le, Son C.1; Hsu, Allen L.2; Borgnia, Mario J.1,2; Yang, Huanghe1; Lee, Seok-Yong1
2019-03-01
发表期刊SCIENCE
ISSN0036-8075
EISSN1095-9203
出版年2019
卷号363期号:6430页码:945-+
文章类型Article
语种英语
国家USA
英文摘要

Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca2+)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), but lack of structural information has thus far precluded a mechanistic understanding of ligand and lipid sensing by TRPM8. Using cryo-electron microscopy, we determined the structures of TRPM8 in complex with the synthetic cooling compound icilin, PIP2, and Ca2+, as well as in complex with the menthol analog WS-12 and PIP2. Our structures reveal the binding sites for cooling agonists and PIP2 in TRPM8. Notably, PIP2 binds to TRPM8 in two different modes, which illustrate the mechanism of allosteric coupling between PIP2 and agonists. This study provides a platform for understanding the molecular mechanism of TRPM8 activation by cooling agents.


领域地球科学 ; 气候变化 ; 资源环境
收录类别SCI-E
WOS记录号WOS:000460194200036
WOS关键词BEAM-INDUCED MOTION ; ION-CHANNEL ; MENTHOL ; REVEALS ; ICILIN ; DESENSITIZATION ; MECHANISM ; PROTEINS ; LIGAND
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
引用统计
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/200861
专题地球科学
资源环境科学
气候变化
作者单位1.Duke Univ, Sch Med, Dept Biochem, Durham, NC 27710 USA;
2.NIEHS, Genome Integr & Struct Biol Lab, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA
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GB/T 7714
Yin, Ying,Le, Son C.,Hsu, Allen L.,et al. Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel[J]. SCIENCE,2019,363(6430):945-+.
APA Yin, Ying,Le, Son C.,Hsu, Allen L.,Borgnia, Mario J.,Yang, Huanghe,&Lee, Seok-Yong.(2019).Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel.SCIENCE,363(6430),945-+.
MLA Yin, Ying,et al."Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel".SCIENCE 363.6430(2019):945-+.
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