Journal article

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

Lisa K Mahdi, Menghang Huang, Xiaoxiao Zhang, Ryohei Thomas Nakano, Leila Brule Kopp, Isabel ML Saur, Florence Jacob, Viera Kovacova, Dmitry Lapin, Jane E Parker, James M Murphy, Kay Hofmann, Paul Schulze-Lefert, Jijie Chai, Takaki Maekawa

Cell Host & Microbe | CELL PRESS | Published : 2020

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 microtu..

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University of Melbourne Researchers

Grants

Awarded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)


Awarded by National Natural Science Foundation of China


Awarded by National Health and Medical Research Council of Australia


Awarded by IRIISS


Funding Acknowledgements

We thank the Max Planck Genome Center Cologne for RNA-seq and Petra Kochner, 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-TLifeact 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.).