A5072606019- Toxin Mechanisms and Immunotoxins
- Histone Deacetylase Inhibitors Research
- Enzyme Structure and Function
- Insect and Pesticide Research
- Advanced Electron Microscopy Techniques and Applications
- Protein Structure and Dynamics
- Photosynthetic Processes and Mechanisms
- Yersinia bacterium, plague, ectoparasites research
- Genomics and Chromatin Dynamics
- Kruppel-like factors research
- Erythrocyte Function and Pathophysiology
- Lipid Membrane Structure and Behavior
- Electron and X-Ray Spectroscopy Techniques
- Signaling Pathways in Disease
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- RNA Research and Splicing
- Insect Resistance and Genetics
- Viral Infections and Immunology Research
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Hemoglobinopathies and Related Disorders
- Mosquito-borne diseases and control
- Biochemical and Molecular Research
- Immune Response and Inflammation
The University of Queensland
2016-2025
Central Queensland University
2024
Global Virus Network
2021
Brisbane School of Theology
2021
Université Joseph Fourier
2012
Institut Curie
2009
Centre National de la Recherche Scientifique
2009
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....
The NADase SARM1 (sterile alpha and TIR motif containing 1) is a key executioner of axon degeneration therapeutic target for several neurodegenerative conditions. We show that potent inhibitor undergoes base exchange with the nicotinamide moiety adenine dinucleotide (NAD
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...
Two antibodies against flaviviruses Flaviviruses are a group of RNA viruses that include the human pathogens dengue virus, Zika and West Nile virus. The envelope protein (E) on virus surface has been target vaccine development, but problems have arisen with E, leading to enhanced infection. Now, Modhiran et al. Biering describe two different bind flavivirus NS1 prevent it from disrupting epithelial cells, which is associated severe disease. Both cross-react multiple proteins. reduce viremia...
Toxin complex (Tc) proteins are a class of bacterial protein toxins that form large, multisubunit complexes. Comprising TcA, B, and C components, they great interest because many exhibit potent insecticidal activity. Here we report the structure novel Tc, Yen-Tc, isolated from bacterium Yersinia entomophaga MH96, which differs majority bacterially derived Tcs in it exhibits oral activity toward broad range insect pests, including diamondback moth ( Plutella xylostella ). We have determined...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 160 million people and resulted in 3.3 deaths, despite the availability of multiple vaccines, world still faces many challenges with their rollout. Here, we use high-density microarray patch (HD-MAP) to deliver a SARS-CoV-2 spike subunit vaccine directly skin. We show that is thermostable on patches, delivery enhancing both cellular antibody immune responses. Elicited antibodies potently neutralize clinically...
Abstract In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This is closely related to Mòjiāng (MojV), and both are divergent the bat-borne HNV members, Nipah (NiV) Hendra (HeV) viruses. The spillover of LayV first instance zoonosis humans outside NiV HeV, highlighting continuing threat this genus poses human health. work, we determine prefusion structures MojV F proteins via cryogenic electron microscopy...
The flavivirus non-structural protein 1 (NS1) is a glycoprotein that secreted as soluble hexameric complex during the course of natural infection. Growing evidence indicates this form NS1 (sNS1) plays significant role in immune evasion and modulation Attempts to determine crystal structure have been unsuccessful date relatively little known about macromolecular organization sNS1 hexamer. Here, we applied single-particle analysis images baculovirus-derived recombinant dengue 2 virus obtained...
Abstract ABC toxins are pore-forming virulence factors produced by pathogenic bacteria. YenTcA is the and membrane binding A subunit of toxin YenTc, insect pathogen Yersinia entomophaga . Here we present cryo-EM structures YenTcA, purified from native source. The soluble pre-pore structure, determined at an average resolution 4.4 Å, reveals a pentameric assembly that in contrast to other characterised formed two TcA-like proteins (YenA1 YenA2) decorated endochitinases (Chi1 Chi2). We also...
The nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native mammalian NuRD complex, combining quantitative mass spectrometry, cross-linking, protein biochemistry, electron microscopy define architecture complex. built from a 2:2:4 (MTA, HDAC, RBBP) module 1:1:1 (MBD, GATAD2, Chromodomain-Helicase-DNA-binding [CHD]) module, displays considerable structural...
Understanding capsid assembly following recombinant expression of viral structural proteins is critical to the design and modification virus-like nanoparticles for biomedical nanotechnology applications. Here, we use plant-based transient Bluetongue virus (BTV) proteins, VP3 VP7, obtain high yields empty green fluorescent protein (GFP)-encapsidating core-like particles (CLPs) from leaves. Single-particle cryo-electron microscopy both types revealed considerable differences in CLP structure...
The rules of engagement between zinc finger transcription factors and DNA have been partly defined by in vitro DNA-binding structural studies, but less is known about how these apply vivo. Here, we demonstrate a missense mutation the second Krüppel-like factor-1 (KLF1) leads to degenerate specificity vivo, resulting ectopic anemia Nan mouse model. We employed ChIP-seq 4sU-RNA-seq identify aberrant events genome wide transcriptional consequences this binding. confirmed novel sequence mutant...
The nucleosome remodeling and deacetylase (NuRD) complex remodels the genome in context of both gene transcription DNA damage repair. It is essential for normal development distributed across multiple tissues organisms ranging from mammals to nematode worms. In common with other chromatin-remodeling complexes, however, its molecular mechanism action not well understood only limited structural information available show how assembled. As a step towards understanding structure NuRD complex, we...
The nucleosome remodeling and deacetylase (NuRD) complex is a chromatin-modifying assembly that regulates gene expression DNA damage repair. Despite its importance, limited structural information describing the complete NuRD available detailed understanding of mechanism therefore lacking. Drawing on from SEC-MALLS, DIA-MS, XLMS, negative-stain EM, X-ray crystallography, NMR spectroscopy, secondary structure predictions, homology models, we applied Bayesian integrative determination to...
Mutations in the transcription factor, KLF1, are common within certain populations of world. Heterozygous missense mutations KLF1 mostly lead to benign phenotypes, but a heterozygous mutation DNA-binding residue (E325K human) results severe Congenital Dyserythropoietic Anemia type IV (CDA IV); i.e. an autosomal-dominant disorder characterized by neonatal hemolysis.To investigate biochemical and genetic mechanism CDA IV, we generated murine erythroid cell lines that harbor tamoxifen-inducible...
Abstract Photosynthetic organisms have developed diverse antennas composed of chromophorylated proteins to increase photon capture. Cryptophyte algae acquired their photosynthetic organelles (plastids) from a red alga by secondary endosymbiosis. Cryptophytes lost the primary algal antenna, phycobilisome, replacing it with unique antenna αβ protomers, where β subunit originates phycobilisome. The origin cryptophyte particularly α subunit, is unknown. Here we show that evolved complex between...
The SP/KLF family of transcription factors harbour three C-terminal C2H2 zinc fingers interspersed by two linkers which confers DNA-binding to a 9-10 bp motif. Mutations in KLF1, the founding member family, are common. Missense mutations linker result mild phenotype. However, when co-inherited with loss-of-function mutations, they severe non-spherocytic hemolytic anemia. We generate mouse model this disease crossing Klf1