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View article: Structural basis of signalling by TIR domain containing proteins
Structural basis of signalling by TIR domain containing proteins Open
The Toll/interleukin-1 receptor (TIR) domain is found in animal, plant and bacterial immune systems, and function through self-association and homotypic interactions with other TIR domains. [1]. It was first described as a protein-protein …
View article: The Arabidopsis TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins
The Arabidopsis TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins Open
The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small…
View article: Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels
Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels Open
The concept of higher-order assembly signalling or signalling by co-operative assembly formation (SCAF) was proposed based on the structures of signalling assemblies formed by proteins featuring domains from the death-fold family and the T…
View article: Chemical inhibition of a bacterial immune system
Chemical inhibition of a bacterial immune system Open
The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-bacteriophage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage im…
View article: Structural basis for TIR domain–mediated innate immune signaling by Toll-like receptor adaptors TRIF and TRAM
Structural basis for TIR domain–mediated innate immune signaling by Toll-like receptor adaptors TRIF and TRAM Open
Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR domain–containing adaptor-inducing interferon-β) and TRAM…
View article: Microcrystal electron diffraction structure of Toll-like receptor 2 TIR-domain-nucleated MyD88 TIR-domain higher-order assembly
Microcrystal electron diffraction structure of Toll-like receptor 2 TIR-domain-nucleated MyD88 TIR-domain higher-order assembly Open
Eukaryotic TIR (Toll/interleukin-1 receptor protein) domains signal via TIR–TIR interactions, either by self-association or by interaction with other TIR domains. In mammals, TIR domains are found in Toll-like receptors (TLRs) and cytoplas…
View article: Structural characterization of TIR-domain signalosomes through a combination of structural biology approaches
Structural characterization of TIR-domain signalosomes through a combination of structural biology approaches Open
The TIR (Toll/interleukin-1 receptor) domain represents a vital structural element shared by proteins with roles in immunity signalling pathways across phyla (from humans and plants to bacteria). Decades of research have finally led to ide…
View article: Structural characterization of macro domain–containing Thoeris antiphage defense systems
Structural characterization of macro domain–containing Thoeris antiphage defense systems Open
Thoeris defense systems protect bacteria from infection by phages via abortive infection. In these systems, ThsB proteins serve as sensors of infection and generate signaling nucleotides that activate ThsA effectors. Silent information reg…
View article: Tetramerization is essential for the enzymatic function of the <i>Pseudomonas aeruginosa</i> virulence factor UDP-glucose pyrophosphorylase
Tetramerization is essential for the enzymatic function of the <i>Pseudomonas aeruginosa</i> virulence factor UDP-glucose pyrophosphorylase Open
Multidrug-resistant bacteria such as the opportunistic pathogen Pseudomonas aeruginosa , which causes life-threatening infections especially in immunocompromised individuals and cystic fibrosis patients, pose an increasing threat to public…
View article: o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2
o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2 Open
Toll-like receptor (TLR) innate immunity signalling protects against pathogens, but excessive or prolonged signalling contributes to a range of inflammatory conditions. Structural information on the TLR cytoplasmic TIR (Toll/interleukin-1 …
View article: Characterisation of Axundead, a novel downstream regulator of Wallerian degeneration
Characterisation of Axundead, a novel downstream regulator of Wallerian degeneration Open
Wallerian degeneration is a conserved program of injury-induced axon degeneration, and is analogous to the blockage of transport that characterises the early stages of many neurodegenerative diseases.In recent years, the TLR adaptor SARM1 …
View article: New Perspectives on Escherichia coli Signal Peptidase I Substrate Specificity: Investigating Why the TasA Cleavage Site Is Incompatible with LepB Cleavage
New Perspectives on Escherichia coli Signal Peptidase I Substrate Specificity: Investigating Why the TasA Cleavage Site Is Incompatible with LepB Cleavage Open
Signal peptidase I is an important drug target, and understanding its substrate is critically important to develop new bacterium-specific drugs. To that end, we have a unique signal peptide that we have shown is refractory to processing by…
View article: SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities
SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities Open
Axons are an essential component of the nervous system, and axon degeneration is an early feature of many neurodegenerative disorders. The NAD + metabolome plays an essential role in regulating axonal integrity. Axonal levels of NAD + and …
View article: Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products
Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products Open
Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants and bacteria, TIR domains are often enzymes that produce isomers of cyclic adenosine 5′-diphosphate–ribose (cADPR) as putative immune signalin…
View article: Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products
Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products Open
Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants and bacteria, TIR domains are enzymes that produce isomers of cyclic ADPR (cADPR) as putative immune signaling molecules. The identity and fun…
View article: Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling
Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling Open
Cyclic adenosine diphosphate (ADP)–ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via nicotinamide adenine dinucleotide (oxidized form) (NAD + ) hydrolysis. We show …
View article: Ucl fimbriae regulation and glycan receptor specificity contribute to gut colonisation by extra-intestinal pathogenic Escherichia coli
Ucl fimbriae regulation and glycan receptor specificity contribute to gut colonisation by extra-intestinal pathogenic Escherichia coli Open
Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut …
View article: Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling
Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling Open
Cyclic ADP ribose (cADPR) isomers are important signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via NAD + hydrolysis, yet their chemical structures are unknown. We show that v-cADPR (2’cADPR) a…
View article: Crystal structure of the Toll/interleukin‐1 receptor (TIR) domain of IL‐1R10 provides structural insights into TIR domain signalling
Crystal structure of the Toll/interleukin‐1 receptor (TIR) domain of IL‐1R10 provides structural insights into TIR domain signalling Open
The Toll/interleukin‐1 receptor (TIR) domains are key innate immune signalling modules. Here, we present the crystal structure of the TIR domain of human interleukin‐1 receptor 10 (IL‐1R10), also called interleukin 1 receptor accessory pro…
View article: Discovery of Cofactor Competitive Inhibitors against the Human Methyltransferase Fibrillarin
Discovery of Cofactor Competitive Inhibitors against the Human Methyltransferase Fibrillarin Open
Fibrillarin (FBL) is an essential and evolutionarily highly conserved S-adenosyl methionine (SAM) dependent methyltransferase. It is the catalytic component of a multiprotein complex that facilitates 2′-O-methylation of ribosomal RNAs (rRN…
View article: Neurotoxin-mediated potent activation of the axon degeneration regulator SARM1.
Neurotoxin-mediated potent activation of the axon degeneration regulator SARM1. Open
Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the NAD-consuming enzyme SARM1. Here, we report a novel activator of SARM1, a metab…