Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues

• Published in: Nature communications Vol. 11; no. 1; p. 3060
• Main Authors: Davies, Katherine A., Fitzgibbon, Cheree, Young, Samuel N., Garnish, Sarah E., Yeung, Wayland, Coursier, Diane, Birkinshaw, Richard W., Sandow, Jarrod J., Lehmann, Wil I. L., Liang, Lung-Yu, Lucet, Isabelle S., Chalmers, James D., Patrick, Wayne M., Kannan, Natarajan, Petrie, Emma J., Czabotar, Peter E., Murphy, James M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.06.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 13/95; 631/45/275; 631/45/535/1266; 631/80/82/2344; 82/80; 82/83; Activation; Animals; Apoptosis; Cell death; Chickens; Crystal structure; Crystallography, X-Ray; Cytoplasm - enzymology; Divergence; Domains; HEK293 Cells; Horses; Humanities and Social Sciences; Humans; Kinases; MAP kinase; Mice; multidisciplinary; Necroptosis; Necrosis - metabolism; Oligomers; Phosphorylation; Protein Conformation; Protein Kinases - chemistry; Rats; Receptor-Interacting Protein Serine-Threonine Kinases - chemistry; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Selectivity; Signal Transduction; Signaling; Smegmamorpha; Swine; U937 Cells; Vertebrates; Xenopus

The MLKL pseudokinase is the terminal effector in the necroptosis cell death pathway. Phosphorylation by its upstream regulator, RIPK3, triggers MLKL’s conversion from a dormant cytoplasmic protein into oligomers that translocate to, and permeabilize, the plasma membrane to kill cells. The precise m...