Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plant resistance (R) genes have evolved specific recognition capabilities in defense against pathogens. The evolution of R gene function and maintenance of R gene diversity within a plant species are therefore of great interest. In the Arabidopsis accession Wassilewskija, the RPP1 region on chromosome 3 contains four genetically linked recognition specificities, conditioning resistance to different isolates of the biotrophic oomycete Peronospora parasitica (downy mildew). We show that three of four tightly linked genes in this region, designated RPP1-WsA, RPP1-WsB, and RPP1-WsC, encode functional products of the NBS-LRR (nucleotide binding site-leucine-rich repeat) R protein class. They possess a TIR (Toll, interleukin-1, resistance) domain that is characteristic of certain other NBS-LRR-type R proteins, but in addition, they have unique hydrophilic or hydrophobic N termini. Together, the three RPP1 genes account for the spectrum of resistance previously assigned to the RPP1 region and thus comprise a complex R locus. The distinct but partially overlapping resistance capabilities conferred by these genes are best explained by the hypothesis that each recognizes a different pathogen avirulence determinant. We present evidence suggesting that the RPP genes at this locus are subject to the same selective forces that have been demonstrated for structurally different LRR-type R genes.
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PMID:Three genes of the Arabidopsis RPP1 complex resistance locus recognize distinct Peronospora parasitica avirulence determinants. 981 93

In a screen for suppressors of npr1-5-based salicylic acid (SA) insensitivity, we isolated a semidominant gain-of-function mutation, designated ssi4, that confers constitutive expression of several PR (pathogenesis-related) genes, induces SA accumulation, triggers programmed cell death, and enhances resistance to bacterial and oomycete pathogens. Through map-based cloning, ssi4 was identified and found to encode a putative protein belonging to the TIR-NBS-LRR (Toll Interleukin1 Receptor-Nucleotide Binding Site-Leu-Rich Repeat) class of R (resistance) proteins. Comparison between ssi4 and the corresponding wild-type sequence revealed a single amino acid substitution in the NBS. Epistasis analysis indicated that SA and EDS1 are required for ssi4-induced PR-1 expression and enhanced disease resistance; they also are required for the increased accumulation of SSI4 and EDS1 transcripts detected in the ssi4 mutant. Although high levels of ssi4 transcripts correlate with the appearance of the mutant phenotype, overexpression of the wild-type SSI4 gene failed to induce stunting, spontaneous lesion formation, or increased PR-1 expression associated with the ssi4 mutation. Thus, the ssi4 phenotype does not appear to be caused by overexpression of this R gene; rather, we propose that the NBS substitution generates a constitutively activated R protein. Furthermore, because SA treatment induced the expression of SSI4 and the closely related TIR-NBS-LRR genes RPP1 and RPS4 but had little effect on the expression of the coiled-coil NBS-LRR genes RPM1 and RPS2, we suggest that SA not only functions as a critical signal for downstream resistance events but also upregulates the expression of certain R genes.
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PMID:A gain-of-function mutation in an Arabidopsis Toll Interleukin1 receptor-nucleotide binding site-leucine-rich repeat type R gene triggers defense responses and results in enhanced disease resistance. 1246 33

Plant immunity to coevolved pathogens relies on the perception of pathogenic effectors by nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins-sophisticated intracellular receptors that have both perception and signaling roles in activating defenses. Given the conserved domain architecture of NLRs, a structural biology perspective is particularly relevant to understanding mechanisms of their activation. Here, we summarize our recent findings on the Arabidopsis resistance protein RPP1, a member of the TIR-NBS-LRR family of plant NLRs that specifically recognizes the cognate effector protein ATR1. To study the basis of RPP1 activation, we have taken advantage of a series of RPP1 and ATR1 alleles that differentially condition resistance. In planta association between the LRR domain of RPP1 and ATR1 only occurs in a resistance-activating combination of alleles, suggesting that a direct interaction between RPP1 and ATR1 protein leads to activation of the NLR (Krasileva et al. 2010). Given critical amino acid residues' locations on the solved ATR1 crystal structure, and variable amino acid residues on the predicted LRR structure of RPP1, we hypothesize that specific "hotspots" of the horseshoe-like LRR fold mediate binding to the ATR1 ligand and that polymorphisms mapping to these surfaces condition differences in allelic recognition specificity. We present docking models of a possible co-complex between RPP1 and ATR1, and we propose that ATR1 binding relieves autoinhibition of RPP1 resistance signaling. This is consistent with current models of activation for both TIR- and CC-type plant NLRs, where conformational changes could lead to NLR oligomerization, nucleotide binding, translocation, and other critical downstream events in triggering immunity.
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PMID:Effector recognition and activation of the Arabidopsis thaliana NLR innate immune receptors. 2317 67