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TitleA disease resistance protein triggers oligomerization of its NLR helper into a hexameric resistosome to mediate innate immunity.
Journal, issue, pagesSci Adv, Vol. 10, Issue 45, Page eadr2594, Year 2024
Publish dateNov 8, 2024
AuthorsJogi Madhuprakash / AmirAli Toghani / Mauricio P Contreras / Andres Posbeyikian / Jake Richardson / Jiorgos Kourelis / Tolga O Bozkurt / Michael W Webster / Sophien Kamoun /
PubMed AbstractNRCs are essential helper NLR (nucleotide-binding domain and leucine-rich repeat) proteins that execute immune responses triggered by sensor NLRs. The resting state of NbNRC2 was recently shown to be ...NRCs are essential helper NLR (nucleotide-binding domain and leucine-rich repeat) proteins that execute immune responses triggered by sensor NLRs. The resting state of NbNRC2 was recently shown to be a homodimer, but the sensor-activated state remains unclear. Using cryo-EM, we determined the structure of sensor-activated NbNRC2, which forms a hexameric inflammasome-like resistosome. Mutagenesis of the oligomerization interface abolished immune signaling, confirming the functional significance of the NbNRC2 resistosome. Comparative structural analyses between the resting state homodimer and sensor-activated homohexamer revealed substantial rearrangements, providing insights into NLR activation mechanisms. Furthermore, structural comparisons between NbNRC2 hexamer and previously reported CC-NLR pentameric assemblies revealed features allowing an additional protomer integration. Using the NbNRC2 hexamer structure, we assessed the recently released AlphaFold 3 for predicting activated CC-NLR oligomers, revealing high-confidence modeling of NbNRC2 and other CC-NLR amino-terminal α1 helices, a region proven difficult to resolve structurally. Overall, our work sheds light on NLR activation mechanisms and expands understanding of NLR structural diversity.
External linksSci Adv / PubMed:39504373 / PubMed Central
MethodsEM (single particle)
Resolution2.9 Å
Structure data

50637

9fp6

EMDB-50637, PDB-9fp6:
Structure of the NbNRC2 hexameric resistosome
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Source
  • nicotiana benthamiana (plant)
KeywordsIMMUNE SYSTEM / Plant immunity / complex

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