MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis
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- Shuzhen Liu
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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- Hua Liu
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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- Andrea Johnston
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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- Sarah Hanna-Addams
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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- Eduardo Reynoso
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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- Yougui Xiang
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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- Zhigao Wang
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
抄録
<jats:title>Significance</jats:title> <jats:p>Necroptosis is a programmed form of necrotic cell death which is implicated in a wide range of human pathological conditions. It is controlled by receptor-interacting protein kinase 3 (RIPK3) and its substrate mixed-lineage kinase domain-like protein (MLKL). Phosphorylated MLKL forms tetramers and translocates to membrane fractions to induce cell death. Here we report that MLKL tetramers further polymerize to form disulfide bond-dependent amyloid-like fibers, which are required for necroptosis. Furthermore, induced polymerization of the MLKL N-terminal domain is sufficient to activate necroptosis without RIPK3. This work reveals a mechanism for MLKL activation and generates exciting directions for necroptosis regulation.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 114 (36), E7450-, 2017-08-21
Proceedings of the National Academy of Sciences