biostudies-literatureSelvaraj MJohn Innes FoundationEuropean Research CouncilWellcome TrustAgricultural Biotechnology Research Center, Academia SinicaBiotechnology and Biological Sciences Research CouncilGatsby Charitable Foundatione3002868https://www.ebi.ac.uk/biostudies/studies/S-EPMC11524475biostudies-literatureUnknown22(10)Nucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 from Nicotiana benthamiana accumulates in vivo as a homodimer that converts into a higher-order oligomer upon activation by its upstream virus disease resistance protein Rx. The cryo-EM structure of NbNRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation and contribute to immune receptor autoinhibition. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network nPLoS biologyActivation of plant immunity through conversion of a helper NLR homodimer into a resistosome.PMC11524475BBS/E/J/000PR9795BB/T006102/1BBS/E/J/000PR9797BBS/E/J/000PR9796BBS/E/J/000PR9798BB/X511055/1Rotation PhD Programme ScholarshipBB/P012574NSTC-111-2628-B-001-023743165BB/V002937/1206166/Z/17/Z202679/Z/16/ZBB/X016382/1Kourelis JBanfield MJKamoun SSelvaraj MSugihara YDerevnina LDe la Concepcion JCBozkurt TOContreras MPLawson DMXie RPai HIbrahim TPetre BWu CHToghani AMaqbool AYuen ELHZhao HfalseActivation of plant immunity through conversion of a helper NLR homodimer into a resistosome.Nucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 from Nicotiana benthamiana accumulates in vivo as a homodimer that converts into a higher-order oligomer upon activation by its upstream virus disease resistance protein Rx. The cryo-EM structure of NbNRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation and contribute to immune receptor autoinhibition. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network n2024-01-01T00:00:00Z2024 Oct2026-07-15T15:32:45.05Z2025-04-06T23:15:01.479ZS-EPMC115244753942324010.1371/journal.pbio.3002868