A5029846556- Calcium signaling and nucleotide metabolism
- Immune Response and Inflammation
- Enzyme Structure and Function
- Plant-Microbe Interactions and Immunity
- Biochemical effects in animals
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Microbial Natural Products and Biosynthesis
- Microbial Metabolism and Applications
- Cancer Research and Treatments
- Natural product bioactivities and synthesis
- RNA and protein synthesis mechanisms
- Sirtuins and Resveratrol in Medicine
- Steroid Chemistry and Biochemistry
- Lipid metabolism and biosynthesis
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Peptides and Activities
- Renin-Angiotensin System Studies
- Cellular Mechanics and Interactions
- NF-κB Signaling Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mitochondrial Function and Pathology
- PARP inhibition in cancer therapy
- 14-3-3 protein interactions
- Cholesterol and Lipid Metabolism
Harvard University
2025
Boston Children's Hospital
2025
The University of Queensland
2019-2023
Chonnam National University
2016-2018
East West University
2013
NAD depletion as pathogen response One way that plants respond to infection is by sacrificing the infected cells. The nucleotide-binding leucine-rich repeat immune receptors responsible for this hypersensitive carry Toll/interleukin-1 receptor (TIR) domains. In two papers, Horsefield et al. and Wan report these TIR domains cleave metabolic cofactor nicotinamide adenine dinucleotide (NAD + ) part of their cell-death signaling in pathogens. Similar links mammalian TIR-containing proteins...
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 that v-cADPR (2′cADPR) v2-cADPR (3′cADPR) cyclized O-glycosidic bond formation between the ribose moieties in ADPR. Structures of 2′cADPR-producing TIR reveal conformational changes lead to an active assembly resembles those Toll-like adaptor domains....
Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants bacteria, TIR domains are often enzymes that produce isomers of cyclic adenosine 5′-diphosphate–ribose (cADPR) as putative immune signaling molecules. The identity functional conservation cADPR isomer signals is unclear. A previous report found a plant could cross-activate the prokaryotic Thoeris TIR–immune system, suggesting TIR-immune signals. Here, we generate autoactive TIRs test converse...
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 adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent signaling. However, the structural basis of domain-based signaling remains unclear. Here, we present cryo-EM structures filaments formed by domains at resolutions 3.3 Å 5.6 Å, respectively. Both reveal...
Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at (LAMs) contain sterol-specific domains [StARkin domain (SD)] multiple targeting modules to specific organelles. Elucidating the structural mechanisms ligand recognition by LAMs important understanding interorganelle communication exchange MCSs. Here, we...
To investigate the antioxidant, antimicrobial, cytotoxic and thrombolytic property of fruits leaves Spondias dulcis (S. dulcis).Methanolic extracts S. were partitioned with chloroform dichloromethane. The antioxidant potential crude extract fractions evaluated in terms total phenolic content, flavonoid DPPH radical scavenging potential, reducing capacity by specific standard procedures. antimicrobial activity was using disc diffusion method. cytotoxicity brine shrimp lethality bioassay...
The Toll/interleukin-1 receptor (TIR) domains are key innate immune signalling modules. Here, we present the crystal structure of TIR domain human interleukin-1 10 (IL-1R10), also called interleukin 1 accessory protein like 2. It is similar to that IL-1R9 (IL-1RAPL1) but shows significant structural differences those from Toll-like receptors (TLRs) and adaptor proteins MyD88 adaptor-like (MAL) MyD88. Interactions in their respective crystals higher-order assemblies (MAL MyD88) reveal...
The fungal pathogen Cryptococcus neoformans is a leading cause of meningoencephalitis in the immunocompromised. As current antifungal treatments are toxic to host, costly, limited their efficacy, and associated with drug resistance, there an urgent need identify vulnerabilities physiology accelerate discovery efforts. Rational design was pioneered de novo purine biosynthesis as end products pathway, ATP GTP, essential for replication, transcription, energy metabolism, same rationale applies...
Abstract 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 unknown. We show that v-cADPR (2’cADPR) v2-cADPR (3’cADPR) cyclized O -glycosidic bond formation between the moieties in ADPR. Structures of (2’cADPR)-producing TIR reveal conformational changes required for active assembly resembles those Toll-like adaptor domains, mutagenesis data...
Abstract Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants bacteria, TIR domains are enzymes that produce isomers of cyclic ADPR (cADPR) as putative immune signaling molecules. The identity functional conservation cADPR isomer signals is unclear. A previous report found a plant could cross-activate the prokaryotic Thoeris TIR-immune system, suggesting signals. Here, we generate auto-active TIRs test converse hypothesis: do also TIR-immunity?...
TIR (Toll/interleukin-1 receptor) domains are widely distributed in animals, plants and bacteria, function through self-association homotypic interactions with other [1].Across phyla, these feature proteins immune functions -TLRs (Toll-like receptors), IL-1Rs (interleukin-1 receptors) their adaptor animals; NLRs (nucleotide-binding, leucine-rich repeat plants; antiphage defence bacteria.Although long assumed to only have protein interaction functions, the across kingdoms also...