Discovery of a Family of Mixed Lineage Kinase Domain-like Proteins in Plants and Their Role in Innate Immune Signaling

Cell Host Microbe. 2020 Dec 9;28(6):813-824.e6. doi: 10.1016/j.chom.2020.08.012. Epub 2020 Oct 13.


HeLo domain-containing mixed lineage kinase domain-like protein (MLKL), a pseudokinase, mediates necroptotic cell death in animals. Here, we report the discovery of a conserved protein family across seed plants that structurally resembles vertebrate MLKL. The Arabidopsis genome encodes three MLKLs (AtMLKLs) with overlapping functions in disease resistance mediated by Toll-interleukin 1-receptor domain intracellular immune receptors (TNLs). The HeLo domain of AtMLKLs confers cell death activity but is dispensable for immunity. Cryo-EM structures reveal a tetrameric configuration, in which the HeLo domain is buried, suggestive of an auto-repressed complex. The mobility of AtMLKL1 along microtubules is reduced by chitin, a fungal immunity-triggering molecule. An AtMLKL1 phosphomimetic variant exhibiting reduced mobility enhances immunity. Coupled with the predicted presence of HeLo domains in plant helper NLRs, our data reveal the importance of HeLo domain proteins for TNL-dependent immunity and argue for a cell death-independent immune mechanism mediated by MLKLs.

Keywords: Cell death; HeLo domain; MLKL; cryo-electron microscopy structures; microtubules; necroptosis; toll-interleukin1-receptor domain intracellular immune receptors.

MeSH terms

  • ADP-ribosyl Cyclase / physiology
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Arabidopsis / physiology*
  • Arabidopsis Proteins / physiology
  • Cell Death
  • Cryoelectron Microscopy
  • Disease Resistance*
  • Genome, Plant
  • Mutation
  • NLR Proteins / physiology*
  • Necroptosis
  • Necrosis
  • Plant Immunity*
  • Plant Proteins / physiology
  • Protein Conformation
  • Protein Domains*
  • Protein Kinases / physiology*
  • Protein Multimerization
  • Signal Transduction


  • Arabidopsis Proteins
  • NLR Proteins
  • Plant Proteins
  • Protein Kinases
  • ADP-ribosyl Cyclase
  • AT1G72930 protein, Arabidopsis