Nature Communications (Nov 2021)

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

  • Yanxiang Meng,
  • Katherine A. Davies,
  • Cheree Fitzgibbon,
  • Samuel N. Young,
  • Sarah E. Garnish,
  • Christopher R. Horne,
  • Cindy Luo,
  • Jean-Marc Garnier,
  • Lung-Yu Liang,
  • Angus D. Cowan,
  • Andre L. Samson,
  • Guillaume Lessene,
  • Jarrod J. Sandow,
  • Peter E. Czabotar,
  • James M. Murphy

DOI
https://doi.org/10.1038/s41467-021-27032-x
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

Read online

The pseudokinase MLKL is activated by the upstream kinase RIPK3 in the necroptotic pathway but the structural basis of MLKL activation is not well understood yet. Here, the authors present the crystal structures of the human RIPK3:MLKL complex and human RIPK3 kinase alone, which reveal structural differences between human and murine RIPK3 and they discuss mechanistic implications.