TIR domains of plant immune receptors are 2′,3′-cAMP/cGMP synthetases mediating cell death

Yu, Dongli; Song, Wen; Tan, Eddie Yong Jun; Liu, Li; Cao, Yu; Jirschitzka, Jan; Li, Ertong; Logemann, Elke; Xu, Chenrui; Huang, Shijia; Jia, Aolin; Chang, Xiaoyu; Han, Zhifu; Wu, Bin; Schulze‐Lefert, Paul; Chai, Jijie

doi:10.1016/j.cell.2022.04.032

Cited by 115 publications

(115 citation statements)

References 89 publications

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“…Thus, plant TIRcontaining proteins appear to constitute a large family of enzymes producing noncanonical and nucleotide-based signaling molecules for regulation of immune and possibly other stress responses. We previously proposed that 2',3'-cAMP/cGMP facilitate self-amplification of EDS1 signaling (37). An outstanding question is how TIR-generated pRib-AMP/ADP or their derivatives intersect with 2',3'-cAMP/cGMP in driving the plant immune response.…”

Section: Discussionmentioning

confidence: 99%

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

Huang

Jia

Song

et al. 2022

Preprint

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Plant nucleotide-binding leucine-rich-repeat receptors (NLRs) with an N-terminal toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR (TNL) signaling requires conserved helper NLRs NRG1 and ADR1 and the lipase-like protein EDS1 that functions as a heterodimer with each of its paralogs PAD4 and SAG101. We show that TIR-containing proteins catalyze production of 2'-(5''-phosphoribosyl)-5'-adenosine mono-/di-phosphate (pRib-AMP/ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP. pRib-ADP binding triggers a conformational change in the PAD4 C-terminal domain to allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity.

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Section: Discussionmentioning

confidence: 99%

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

Huang

Jia

Song

et al. 2022

Preprint

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“…Our previous study showed that TIR proteins can hydrolyze ATP/GTP ( 35 ). We therefore tested whether pRib-AMP/ADP (which efficiently activate EDS1-PAD4) ( 28 ) can be produced through RPS4-TIR hydrolysis of ADPr-ATP or di-ADPR.…”

Section: Identification Of a Small Molecule Specifically Activating E...mentioning

confidence: 99%

TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity

Jia

Huang

Song

et al. 2022

Preprint

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Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/Interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded NADases produce signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR sub-classes. Here we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) via ADPR polymerase-like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively. Specific binding of di-ADPR or ADPr-ATP allosterically promotes EDS1-SAG101 interaction with helper NLR N requirement gene 1A (NRG1A) in vitro and in planta. Our data reveal an enzymatic activity of TIRs that enables specific activation of the EDS1-SAG101-NRG1 immunity branch.

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“…Upon effector activation, NLRs oligomerize and form “resistosome” complexes to activate calcium influx (CNLs) or to activate TNL NADase activity. The latter generates small molecules that activate an EDS1 anchored complex to initiate cell death and defense through the calcium channel function of a class of ‘helper’ NLRs called RNLs (Bi et al, 2021; Huang et al, 2022; Jacob et al, 2021; Martin et al, 2020; Ma et., 2020; Jubic et al, 2019; Wan et al, 2019; Wang et al, 2019a, 2019b; Yu et al, 2021). NLRs can function as singletons, in genetically linked pairs, or in immune networks (Adachi et al, 2019; Wu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Allelic variation in theArabidopsisTNL CHS3/CSA1 immune receptor pair reveals two functional regulatory modes

Yang

Kim

Çevik

et al. 2022

Preprint

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Some plant NLR immune receptors are encoded in head-to-head pairs that function together. Alleles of the NLR pair CHS3/CSA1 form three clades. The clade 1 sensor CHS3 contains an integrated domain (ID) with homology to regulatory domains, which is lacking in clades 2 and 3. We defined two regulatory modes for CHS3/CSA1 pairs. One is likely mediated by effector binding to the clade 1 ID of CHS3 and the other relies on CHS3/CSA1 pairs from all clades detecting effector modification of an associated pattern recognition receptor. We suggest that an ancestral Arabidopsis CHS3/CSA1 pair gained a second recognition specificity and regulatory mechanism through ID acquisition, while retaining its original specificity as a ‘Guard’ against perturbation of pattern recognition receptor targeting by a pathogen effector. This likely comes with a cost, since both ID and non-ID alleles of the pair persist in diverse Arabidopsis populations through balancing selection.SummaryWe dissect a novel case where two regulatory modes emerged across three clades of the co-evolved CHS3/CSA1 plant immune receptor pairs, which features recruitment of an integrated domain (ID) into the clade 1 CHS3 alleles. Pre- and post-ID integration alleles maintain functionality; balancing selection maintains both in the Arabidopsis pan-genome.

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TIR domains of plant immune receptors are 2′,3′-cAMP/cGMP synthetases mediating cell death

Cited by 115 publications

References 89 publications

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity

Allelic variation in theArabidopsisTNL CHS3/CSA1 immune receptor pair reveals two functional regulatory modes

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