MLKL forms cation channels
文献类型:期刊论文
作者 | Xia, Bingqing2; Fang, Sui2; Chen, Xueqin2; Hu, Hong1; Chen, Peiyuan2; Wang, Huayi1; Gao, Zhaobing2![]() |
刊名 | CELL RESEARCH
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出版日期 | 2016-05 |
卷号 | 26期号:5页码:517-528 |
关键词 | MLKL magnesium channel bilayer lipid membrane cation channel necroptosis |
ISSN号 | 1001-0602 |
DOI | 10.1038/cr.2016.26 |
文献子类 | Article |
英文摘要 | The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg2+ rather than Ca2+ in the presence of Na+ and K+. Moreover, the N-terminal domain containing six helices (H1-H6) is sufficient to form channels. Using the substituted cysteine accessibility method, we further determine that helix H1, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels. |
WOS关键词 | TUMOR-NECROSIS-FACTOR ; MIXED LINEAGE KINASE ; DOMAIN-LIKE PROTEIN ; RAT-HEART MITOCHONDRIA ; PROGRAMMED NECROSIS ; CELL-DEATH ; MAGNESIUM HOMEOSTASIS ; CRYSTAL-STRUCTURE ; MG2+ ; NECROPTOSIS |
资助项目 | State Key Program of Basic Research of China[2013CB910604] ; National Natural Science Foundation of China[61327014] ; National Natural Science Foundation of China[61175103] ; National Natural Science Foundation of China[61433017] ; National Natural Science Foundation of China[31571427] ; External Cooperation Program of BIC, Chinese Academy of Sciences[1536631KYSB20130003] |
WOS研究方向 | Cell Biology |
语种 | 英语 |
CSCD记录号 | CSCD:5707286 |
WOS记录号 | WOS:000377449200004 |
出版者 | INST BIOCHEMISTRY & CELL BIOLOGY |
源URL | [http://119.78.100.183/handle/2S10ELR8/276048] ![]() |
专题 | 神经药理学研究国际科学家工作站 |
通讯作者 | Wang, Huayi; Gao, Zhaobing |
作者单位 | 1.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; |
推荐引用方式 GB/T 7714 | Xia, Bingqing,Fang, Sui,Chen, Xueqin,et al. MLKL forms cation channels[J]. CELL RESEARCH,2016,26(5):517-528. |
APA | Xia, Bingqing.,Fang, Sui.,Chen, Xueqin.,Hu, Hong.,Chen, Peiyuan.,...&Gao, Zhaobing.(2016).MLKL forms cation channels.CELL RESEARCH,26(5),517-528. |
MLA | Xia, Bingqing,et al."MLKL forms cation channels".CELL RESEARCH 26.5(2016):517-528. |
入库方式: OAI收割
来源:上海药物研究所
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