PT  - JOURNAL ARTICLE
AU  - Lisa Mahdi
AU  - Menghang Huang
AU  - Xiaoxiao Zhang
AU  - Ryohei Thomas Nakano
AU  - Leïla Brulé Kopp
AU  - Isabel M.L. Saur
AU  - Florence Jacob
AU  - Viera Kovacova
AU  - Dmitry Lapin
AU  - Jane E. Parker
AU  - James M. Murphy
AU  - Kay Hofmann
AU  - Paul Schulze-Lefert
AU  - Jijie Chai
AU  - Takaki Maekawa
TI  - Plant mixed lineage kinase domain-like proteins limit biotrophic pathogen growth
AID  - 10.1101/681015
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 681015
4099  - http://biorxiv.org/content/early/2019/06/25/681015.short
4100  - http://biorxiv.org/content/early/2019/06/25/681015.full
AB  - Mixed lineage kinase domain-like (MLKL) protein mediates necroptotic cell death in vertebrates. We report here the discovery of a conserved protein family across seed plants that is structurally homologous to vertebrate MLKL. The Arabidopsis thaliana genome encodes three MLKLs with overlapping functions in limiting growth of obligate biotrophic fungal and oomycete pathogens. Although displaying a cell death activity mediated by N-terminal helical bundles, termed HeLo domain, AtMLKL-dependent immunity can be separated from host cell death. Cryo-electron microscopy structures of AtMLKLs reveal a tetrameric configuration, in which the pseudokinase domain and brace region bury the HeLo-domains, indicative of an auto-repressed complex. We also show the association of two AtMLKLs with microtubules. These findings, coupled with resistance-enhancing activity and altered microtubule association of a phosphomimetic mutation in the pseudokinase domain of AtMLKL1, point to a cell death-independent immunity mechanism.One Sentence Summary Plants have a protein family that is structurally homologous to vertebrate mixed lineage kinase domain-like protein, which induces necroptotic cell death, but these plant proteins can confer immunity without host cell death.