MLKL forms cation channels

doi:10.1038/cr.2016.26

	MLKL forms cation channels
	Xia, Bingqing 1; Fang, Sui 1; Chen, Xueqin 1; Hu, Hong2 ; Chen, Peiyuan 1; Wang, Huayi2 ; Gao, Zhaobing 1
	2016-05
发表期刊	CELL RESEARCH
ISSN	1001-0602
卷号	26 期号:5 页码:517-528
发表状态	已发表
DOI	10.1038/cr.2016.26
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.
关键词	MLKL magnesium channel bilayer lipid membrane cation channel necroptosis
收录类别	SCI
语种	英语
资助项目	External Cooperation Program of BIC, Chinese Academy of Sciences[1536631KYSB20130003]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000377449200004
出版者	NATURE PUBLISHING GROUP
WOS关键词	MIXED LINEAGE KINASE ; DOMAIN-LIKE PROTEIN ; TUMOR NECROSIS FACTOR ; PROGRAMMED NECROSIS ; CRYSTAL-STRUCTURE ; CELL-DEATH ; MG2+ ; NECROPTOSIS ; MAGNESIUM ; RIP3
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1850
专题	生命科学与技术学院生命科学与技术学院_PI研究组_王华翌组生命科学与技术学院_博士生
通讯作者	Wang, Huayi; Gao, Zhaobing
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
通讯作者单位	生命科学与技术学院
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.