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Mahdi, L.K., Huang, M., Zhang, X., Nakano, R.T., Kopp, L.B., Saur, I.M.L., Jacob, F., Kovacova, V., Lapin, D., Parker, J.E., Murphy, J.M., Hofmann, K., Schulze-Lefert, P., Chai, J., Maekawa, T.

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

Abstract

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 Arabidospsis genome encodes three MLKLs (AtMLKLs) with overlapping functions in disease resistance mediated by Toll-interleukin 1-receptor domain intracellular immune receptors (TNLs). HeLo domain of AtMLKLs confers cell death activity but is dispensable for immunity. Cryo-EM structures reveal a tetrameric configuration, wherein the HeLo domain is buried, suggestive of an auto-repressed complex. The mobility of AtMLKL 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 the TNL-dependent immunity and argue for a cell death-independent immune mechanism mediated by MLKLs.

Rad more at: Cell Host & Microbe