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学科主题: 药学
题名:
Divalent cations activate TRPV1 through promoting conformational change of the extracellular region
作者: Yang, Fan1; Ma, Linlin1,2; Cao, Xu1,3; Wang, KeWei3,4; Zheng, Jie1
刊名: JOURNAL OF GENERAL PHYSIOLOGY
发表日期: 2014
DOI: 10.1085/jgp.201311024
卷: 143, 期:1, 页:91-103
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Physiology
研究领域[WOS]: Physiology
关键词[WOS]: CAPSAICIN RECEPTOR TRPV1 ; EXTERNAL PROTONATION SITES ; NUCLEOTIDE-GATED CHANNELS ; GO POTASSIUM CHANNELS ; BARIUM PERMEATION ; ION CHANNELS ; PORE TURRET ; K+ CHANNEL ; VOLTAGE ; CELLS
英文摘要:

Divalent cations Mg2+ and Ba2+ selectively and directly potentiate transient receptor potential vanilloid type 1 heat activation by lowering the activation threshold into the room temperature range. We found that Mg2+ potentiates channel activation only from the extracellular side; on the intracellular side, Mg2+ inhibits channel current. By dividing the extracellularly accessible region of the channel protein into small segments and perturbing the structure of each segment with sequence replacement mutations, we observed that the S1-S2 linker, the S3-S4 linker, and the pore turret are all required for Mg2+ potentiation. Sequence replacements at these regions substantially reduced or eliminated Mg2+-induced activation at room temperature while sparing capsaicin activation. Heat activation was affected by many, but not all, of these structural alternations. These observations indicate that extracellular linkers and the turret may interact with each other. Site-directed fluorescence resonance energy transfer measurements further revealed that, like heat, Mg2+ also induces structural changes in the pore turret. Interestingly, turret movement induced by Mg2+ precedes channel activation, suggesting that Mg2+-induced conformational change in the extracellular region most likely serves as the cause of channel activation instead of a coincidental or accommodating structural adjustment.

语种: 英语
所属项目编号: R01NS072377 ; B07001 ; 2013CB531302 ; 81221002
项目资助者: National Institutes of Health ; UC Davis Health System Research Award ; Ministry of Education of China 111 Project ; Ministry of Science and Technology of China ; National Science Foundation of China ; Australian National Health and Medical Research Council fellowship ; American Heart Association predoctoral fellowship
WOS记录号: WOS:000329129800012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57685
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA
2.Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia
3.Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
4.Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China

Recommended Citation:
Yang, Fan,Ma, Linlin,Cao, Xu,et al. Divalent cations activate TRPV1 through promoting conformational change of the extracellular region[J]. JOURNAL OF GENERAL PHYSIOLOGY,2014,143(1):91-103.
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