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DOI | 10.1126/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
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
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 |
推荐引用方式 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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