A5017450037- interferon and immune responses
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Polymer crystallization and properties
- Polymer Nanocomposites and Properties
- Ubiquitin and proteasome pathways
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Bacterial biofilms and quorum sensing
- RNA regulation and disease
- Advanced biosensing and bioanalysis techniques
- Advanced Wireless Communication Techniques
- Protease and Inhibitor Mechanisms
- Inflammasome and immune disorders
- Structural Behavior of Reinforced Concrete
- Hydrology and Watershed Management Studies
- Antibiotic Resistance in Bacteria
- Fiber-reinforced polymer composites
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
Nanyang Technological University
2012-2025
Université Bourgogne Franche-Comté
2025
Chongqing University
2006-2024
Inner Mongolia University of Technology
2024
Wuhan University of Technology
2012-2024
China Electronics Technology Group Corporation
2019-2023
Beihang University
2022
Xi'an University of Technology
2021
Boston VA Research Institute
2020
Harvard University
2011-2020
MDA5, an RIG-I-like helicase, is a conserved cytoplasmic viral RNA sensor, which recognizes dsRNA from wide-range of viruses in length-dependent manner. It has been proposed that MDA5 forms higher-order structures upon recognition or during antiviral signaling, however the organization and nature this oligomeric state unknown. We report here cooperatively assembles into filamentous oligomer composed repeating segmental arrangement dimers along length dsRNA. Binding to stimulates its ATP...
Breaking and forming peptidyl bonds are fundamental biochemical reactions in protein chemistry. Unlike proteases that abundantly available, fast-acting ligases rare. OaAEP1 is an enzyme isolated from the cyclotide-producing plant oldenlandia affinis displayed weak peptide cyclase activity, despite having a similar structural fold with other asparaginyl endopeptidases (AEP). Here we report first atomic structure of OaAEP1, at resolution 2.56 Å, its preactivation form. Our analysis this...
Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND)1-7. In resting cells, dipeptidyl peptidases DPP8 and DPP9 interact with FIIND suppress spontaneous activation8,9; however, mechanisms through which this occurs remain unknown. Here we present structural biochemical evidence that full-length rat (rNLRP1) (rDPP9) form a 2:1 complex...
Human NLRP1 (NACHT, LRR, and PYD domain-containing protein 1) is an innate immune sensor predominantly expressed in the skin airway epithelium. Here, we report that human senses ultraviolet B (UVB)- toxin-induced ribotoxic stress response (RSR). Biochemically, RSR leads to direct hyperphosphorylation of a human-specific disordered linker region (NLRP1 DR ) by MAP3K20/ZAKα kinase its downstream effector, p38. Mutating single ZAKα phosphorylation site abrogates UVB- ribotoxin-driven pyroptosis...
Abstract Nucleotide-binding leucine-rich repeat (NLR) proteins play a pivotal role in plant immunity by recognizing pathogen effectors 1,2 . Maintaining balanced immune response is crucial, as excessive NLR expression can lead to unintended autoimmunity 3,4 Unlike most NLRs, the required for cell death 2 (NRC2) belongs small group characterized constitutively high without self-activation 5 The mechanisms underlying NRC2 autoinhibition and activation are not yet understood. Here we show that...
The influx of genomic sequence information has led to the concept structural proteomics, determination protein structures on a genome-wide scale. Here we describe an approach proteomics small proteins using NMR spectroscopy. Over 500 from several organisms were cloned, expressed, purified, and evaluated by NMR. Although there was variability among proteomes, overall 20% these found be readily amenable structure determination. sample preparation centralized in one facility, distributive used...
Chromatin organization and composition impart sophisticated regulatory features critical to eukaryotic genomic function. Although DNA sequence-dependent histone octamer binding is important for nucleosome activity, many aspects of this phenomenon have remained elusive. We studied structure stability with diverse sequences, including Widom 601 derivatives the highest known affinities, establish a simple model behind mechanics sequence dependency. This uncovers unique but unexpected role TA...
His-tones are not ruth-less: A ruthenium anticancer agent, RAPTA-C, was found to associate with chromatin in cancer cells and form stable, well-defined adducts the nucleosome core at specific histone protein sites (see picture). This illuminates macromolecular binding properties of this antimetastasis agent indicates potential for developing metallodrugs site-selective targeting chromatin.
The viral sensor MDA5 distinguishes between cellular and dsRNAs by length-dependent recognition in the range of ∼0.5–7 kb. ability to discriminate dsRNA length at this scale sets apart from other receptors immune system. We have shown previously that forms filaments along disassemble upon ATP hydrolysis. Here, we demonstrate filament formation alone is insufficient explain its specificity, because intrinsic affinity for depends only moderately on length. Instead, uses a combination end...
The recent development of chemical and bio-conjugation techniques allows for the engineering various protein polymers. However, most polymerization process is difficult to control. To meet this challenge, we develop an enzymatic procedure build polyprotein using combination a strict ligase OaAEP1 (Oldenlandia affinis asparaginyl endopeptidases 1) protease TEV (tobacco etch virus). We firstly demonstrate use OaAEP1-alone sequence-uncontrolled ubiquitin covalently immobilize coupled on...
Abstract Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling activating the inflammasome complex. Closely related sensor NLRP1 CARD8 undergo unique auto-proteolysis-dependent activation are implicated in auto-inflammatory diseases; however, their mechanisms of not understood. Here we report structural basis how domains (FIIND UPA -CARD) self-oligomerize to assemble distinct complexes. Recombinant FIIND -CARD forms a two-layered filament,...
Catalytic concentrations of apigenin (a flavone containing a phenol B ring) and naringin or naringenin (flavanones caused extensive GSH oxidation at physiological pH in the presence peroxidase. Only catalytic H2O2 were required, indicating redox cycling mechanism that generated was involved. Extensive oxygen uptake ensued, extent which proportional to GSSG markedly increased by superoxide dismutase. These results suggest prooxidant phenoxyl radicals formed these flavonoids co-oxidized form...
NleG homologues constitute the largest family of type 3 effectors delivered by pathogenic E. coli, with fourteen members in enterohaemorrhagic (EHEC) O157:H7 strain alone. Identified recently as part non-LEE-encoded (Nle) effector set, this remained uncharacterised and shared no sequence homology to other proteins including those known function. The C-terminal domain NleG2-3 (residues 90 191) is most conserved region was solved NMR. Structural analysis structure revealed presence a RING...
The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase classical resistance mechanism. Many employ quorum sensing (QS) to govern production virulence factors and formation drug-resistant biofilms. Targeting mechanism QS proven be a functional conventional control infections. However, presence multiple systems in individual bacterial species poses challenge this approach. Quorum inhibitors (QSI) quenching enzymes (QQE)...
Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and transduced specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an protein that critical for signal propagation of the Nucleotide-binding-oligomerization-domain-containing 1/2 (NOD1 NOD2). Dysregulation this signaling pathway leads to defects detection some cases autoimmune diseases. Here, we show...