9FP6

Structure of the NbNRC2 hexameric resistosome

Summary for 9FP6

• Entry DOI: 10.2210/pdb9fp6/pdb
• EMDB information: 50637
• Descriptor: NRC2a, ADENOSINE-5'-TRIPHOSPHATE (2 entities in total)
• Functional Keywords: plant immunity, complex, immune system
• Biological source: Nicotiana benthamiana
• Total number of polymer chains: 6
• Total formula weight: 610663.09

Authors

Webster, M.W.,Madhuprakash, J.,Kamoun, S. (deposition date: 2024-06-13, release date: 2024-07-03, Last modification date: 2025-07-16)

Primary citation

Madhuprakash, J.,Toghani, A.,Contreras, M.P.,Posbeyikian, A.,Richardson, J.,Kourelis, J.,Bozkurt, T.O.,Webster, M.W.,Kamoun, S.
A disease resistance protein triggers oligomerization of its NLR helper into a hexameric resistosome to mediate innate immunity.
Sci Adv, 10:eadr2594-eadr2594, 2024

PubMed Abstract: 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.

PubMed: 39504373
DOI: 10.1126/sciadv.adr2594

Experimental method

ELECTRON MICROSCOPY (2.9 Å)