Nature Communications (Jun 2018)

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis

  • Emma J. Petrie,
  • Jarrod J. Sandow,
  • Annette V. Jacobsen,
  • Brian J. Smith,
  • Michael D. W. Griffin,
  • Isabelle S. Lucet,
  • Weiwen Dai,
  • Samuel N. Young,
  • Maria C. Tanzer,
  • Ahmad Wardak,
  • Lung-Yu Liang,
  • Angus D. Cowan,
  • Joanne M. Hildebrand,
  • Wilhelmus J. A. Kersten,
  • Guillaume Lessene,
  • John Silke,
  • Peter E. Czabotar,
  • Andrew I. Webb,
  • James M. Murphy

DOI
https://doi.org/10.1038/s41467-018-04714-7
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 15

Abstract

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RIPK3-mediated phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.