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

• Published in: Cell host & microbe 2020-12, Vol.28 (6), p.813-824.e6
• Main Authors: Mahdi, Lisa K., Huang, Menghang, Zhang, Xiaoxiao, Nakano, Ryohei Thomas, Kopp, Leïla Brulé, Saur, Isabel M.L., Jacob, Florence, Kovacova, Viera, Lapin, Dmitry, Parker, Jane E., Murphy, James M., Hofmann, Kay, Schulze-Lefert, Paul, Chai, Jijie, Maekawa, Takaki
• Format: Article
• Language: English
• Subjects: Cell death; cryo-electron microscopy structures; HeLo domain; Life Sciences; Microbiology and Parasitology; microtubules; MLKL; necroptosis; toll-interleukin1-receptor domain intracellular immune receptors; Virology
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2020.08.012

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. [Display omitted] •Plant genomes encode a family of proteins resembling animal necroptosis mediator MLKL•Arabidopsis MLKLs (AtMLKLs) promote pathogen resistance mediated by TIR-type NLRs•Cryo-EM structure of AtMLKL reveals tetramers, which represents an auto-repressed state•AtMLKLs HeLo domain can elicit cell death but this is dispensable for immune function Mahdi et al. discover a protein family resembling the vertebrate necroptosis mediator MLKL in plants. Arabidopsis MLKLs (AtMLKLs) promote pathogen resistance mediated by TIR-type NLRs. Structural analysis suggests an auto-repressed tetrameric state and although AtMLKL’s HeLo domain can elicit cell death, this function is dispensable for immunity.