Divalent cations activate TRPV1 through promoting conformational change of the extracellular region | |
Yang, Fan ; Ma, Linlin ; Cao, Xu ; Wang, KeWei ; Zheng, Jie | |
刊名 | journal of general physiology |
2014 | |
关键词 | CAPSAICIN RECEPTOR TRPV1 EXTERNAL PROTONATION SITES NUCLEOTIDE-GATED CHANNELS GO POTASSIUM CHANNELS BARIUM PERMEATION ION CHANNELS PORE TURRET K+ CHANNEL VOLTAGE CELLS |
DOI | 10.1085/jgp.201311024 |
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.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000329129800012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Physiology; SCI(E); 10; ARTICLE; wangkw@bjmu.edu.cn; jzheng@ucdavis.edu; 1; 91-103; 143 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/390616] |
专题 | 心理与认知科学学院 |
推荐引用方式 GB/T 7714 | 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. |
APA | Yang, Fan,Ma, Linlin,Cao, Xu,Wang, KeWei,&Zheng, Jie.(2014).Divalent cations activate TRPV1 through promoting conformational change of the extracellular region.journal of general physiology. |
MLA | Yang, Fan,et al."Divalent cations activate TRPV1 through promoting conformational change of the extracellular region".journal of general physiology (2014). |
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