@article{f032aaaf3d2a41679d66fc79a6213ae4,
title = "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 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, cryo-electron microscopy structures, HeLo domain, microtubules, MLKL, necroptosis, toll-interleukin1-receptor domain intracellular immune receptors",
author = "Mahdi, {Lisa K.} and Menghang Huang and Xiaoxiao Zhang and Nakano, {Ryohei Thomas} and Kopp, {Le{\"i}la Brul{\'e}} and Saur, {Isabel M.L.} and Florence Jacob and Viera Kovacova and Dmitry Lapin and Parker, {Jane E.} and Murphy, {James M.} and Kay Hofmann and Paul Schulze-Lefert and Jijie Chai and Takaki Maekawa",
note = "Funding Information: We thank the Max Planck Genome Center Cologne for RNA-seq and Petra K{\"o}chner, Sabine Haigis, Jaqueline Bautor, and Makoto Yoshikawa-Maekawa for technical assistance and Neysan Donnelly for editing the manuscript. We also thank Hirofumi Nakagami, Ton Timmers, Masayoshi Hashimoto, Hamid Kashkar, and Manolis Pasparakis for helpful suggestions. We also thank Takashi Hashimoto and Stefanie Sprunck for the mCherry-MAP4 and tagRFP-T-Lifeact vectors, respectively. We also thank Xiaomei Li (Tsinghua University) for technical support during EM image acquisition. We thank the Tsinghua University Branch of the China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, SFB-1403–414786233 to D.L., J.E.P., K.H., P.S.-L., J.C., and T.M.), a grant from the University of Cologne Centre of Excellence in Plant Sciences (T.M.), the National Natural Science Foundation of China ( 31421001 to J.C.), the National Health and Medical Research Council of Australia (fellowships 1105754 and 1172929 ; project 1124735 ) and IRIISS ( 9000587 ), the Victorian State Government Operational Infrastructure Support scheme (J.M.M.), and the Alexander von Humboldt Foundation (a Humboldt professorship to J.C.). Funding Information: We thank the Max Planck Genome Center Cologne for RNA-seq and Petra K?chner, Sabine Haigis, Jaqueline Bautor, and Makoto Yoshikawa-Maekawa for technical assistance and Neysan Donnelly for editing the manuscript. We also thank Hirofumi Nakagami, Ton Timmers, Masayoshi Hashimoto, Hamid Kashkar, and Manolis Pasparakis for helpful suggestions. We also thank Takashi Hashimoto and Stefanie Sprunck for the mCherry-MAP4 and tagRFP-T-Lifeact vectors, respectively. We also thank Xiaomei Li (Tsinghua University) for technical support during EM image acquisition. We thank the Tsinghua University Branch of the China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, SFB-1403?414786233 to D.L. J.E.P. K.H. P.S.-L. J.C. and T.M.), a grant from the University of Cologne Centre of Excellence in Plant Sciences (T.M.), the National Natural Science Foundation of China (31421001 to J.C.), the National Health and Medical Research Council of Australia (fellowships 1105754 and 1172929; project 1124735) and IRIISS (9000587), the Victorian State Government Operational Infrastructure Support scheme (J.M.M.), and the Alexander von Humboldt Foundation (a Humboldt professorship to J.C.). T.M. conceptualized the project; L.M. M.H. X.Z. R.T.N. L.B.K. I.M.L.S. F.J. V.K. D.L. K.H. and T.M. performed the investigations; J.E.P. J.M.M. P.S.-L. J.C. and T.M. validated the data; J.E.P. J.M.M. P.S.-L. J.C. and T.M. supervised the work; J.C. and T.M. wrote the original draft of the manuscript; J.E.P. P.S.-L. and J.M.M. reviewed and edited the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = dec,
day = "9",
doi = "10.1016/j.chom.2020.08.012",
language = "English",
volume = "28",
pages = "813--824",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "6",
}