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MLKL forms cation channels

delete2016-04-01
delete149
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OA
AI
B
Bingqing Xia
S
Sui Fang
X
Xueqin Chen
胡红 封面图
胡红 (Hong Hu)
C
Chen, Peiyuan
H
Huayi Wang *
高
高召兵 (Zhaobing Gao) *
DOI:10.1038/cr.2016.26delete
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摘要

摘要

En 中文
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.
Keyword:
MLKL
magnesium channel
bilayer lipid membrane
cation channel
necroptosis
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Cell Research
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S
shanghai institute of materia medica, cas
学者数:
3.6K
论文数: 2.4K
被引数: 5
C
chinese academy of sciences
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论文数: 45.0W
被引数: 704
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