Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis

• Published in: Nature communications Vol. 12; no. 1; p. 6783
• Main Authors: Meng, Yanxiang, Davies, Katherine A., Fitzgibbon, Cheree, Young, Samuel N., Garnish, Sarah E., Horne, Christopher R., Luo, Cindy, Garnier, Jean-Marc, Liang, Lung-Yu, Cowan, Angus D., Samson, Andre L., Lessene, Guillaume, Sandow, Jarrod J., Czabotar, Peter E., Murphy, James M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/275; 631/535/1266; 631/80/82/2344; 82/80; 82/83; 96; Animals; Apoptosis; Cell death; Cell Death - genetics; Cell Death - physiology; Conformation; Crystal structure; HT29 Cells; Humanities and Social Sciences; Humans; Inflammatory diseases; Kinases; Mice; Mortality; multidisciplinary; Necroptosis; Necroptosis - genetics; Necroptosis - physiology; Phosphorylation; Protein Conformation; Protein Interaction Domains and Motifs; Protein Kinases - chemistry; Protein Kinases - genetics; Protein Kinases - metabolism; Receptor-Interacting Protein Serine-Threonine Kinases - chemistry; Receptor-Interacting Protein Serine-Threonine Kinases - genetics; Receptor-Interacting Protein Serine-Threonine Kinases - metabolism; Recombinant Proteins; Science; Science (multidisciplinary); Signal Transduction; Upstream

The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pse...