RPW8/HR repeats control NLR activation in Arabidopsis thaliana

PLoS Genet. 2019 Jul 25;15(7):e1008313. doi: 10.1371/journal.pgen.1008313. eCollection 2019 Jul.


In many plant species, conflicts between divergent elements of the immune system, especially nucleotide-binding oligomerization domain-like receptors (NLR), can lead to hybrid necrosis. Here, we report deleterious allele-specific interactions between an NLR and a non-NLR gene cluster, resulting in not one, but multiple hybrid necrosis cases in Arabidopsis thaliana. The NLR cluster is RESISTANCE TO PERONOSPORA PARASITICA 7 (RPP7), which can confer strain-specific resistance to oomycetes. The non-NLR cluster is RESISTANCE TO POWDERY MILDEW 8 (RPW8) / HOMOLOG OF RPW8 (HR), which can confer broad-spectrum resistance to both fungi and oomycetes. RPW8/HR proteins contain at the N-terminus a potential transmembrane domain, followed by a specific coiled-coil (CC) domain that is similar to a domain found in pore-forming toxins MLKL and HET-S from mammals and fungi. C-terminal to the CC domain is a variable number of 21- or 14-amino acid repeats, reminiscent of regulatory 21-amino acid repeats in fungal HET-S. The number of repeats in different RPW8/HR proteins along with the sequence of a short C-terminal tail predicts their ability to activate immunity in combination with specific RPP7 partners. Whether a larger or smaller number of repeats is more dangerous depends on the specific RPW8/HR autoimmune risk variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics*
  • Arabidopsis / microbiology
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / genetics*
  • Ascomycota / pathogenicity
  • Disease Resistance
  • Immunity, Innate
  • Plant Diseases / microbiology
  • Repetitive Sequences, Nucleic Acid


  • Arabidopsis Proteins
  • RPP7 protein, Arabidopsis
  • RPW8.1 protein, Arabidopsis

Grant support

This study was supported by a Marie Curie postdoctoral fellowship (2014-655295, https://ec.europa.eu/research/mariecurieactions/actions/individual-fellowships_en) to RW, the Academic Research Fund from the National University of Singapore (R-154-000-B33-114, https://www.nrf.gov.sg/) to EC, ERC Advanced Grant IMMUNEMESIS (340602, https://erc.europa.eu/funding/advanced-grants), the Deutsche Forschungsgemeinschaft through the Collaborative Research Center (CRC1101, https://www.dfg.de/en/research_funding/programmes/coordinated_programmes/collaborative_research_centres/), and The Max Planck Society (https://www.mpg.de/en) to DW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.