A5017125528- Axon Guidance and Neuronal Signaling
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Photosynthetic Processes and Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Advanced Electron Microscopy Techniques and Applications
- HIV Research and Treatment
- Cancer-related gene regulation
- Viral Infections and Immunology Research
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Virus-based gene therapy research
- ATP Synthase and ATPases Research
- Viral gastroenteritis research and epidemiology
- Streptococcal Infections and Treatments
- Toxoplasma gondii Research Studies
- Signaling Pathways in Disease
- HIV/AIDS drug development and treatment
- Asymmetric Synthesis and Catalysis
- Autophagy in Disease and Therapy
- Herpesvirus Infections and Treatments
- Bacteriophages and microbial interactions
- Protein Structure and Dynamics
- Oxidative Organic Chemistry Reactions
- Clostridium difficile and Clostridium perfringens research
Centre for Human Genetics
2016-2025
University of Oxford
2016-2025
University of Hong Kong
2023-2025
Nanjing Medical University
2024-2025
Jiangsu Province Hospital
2024-2025
Hebei North University
2025
Sichuan University of Science and Engineering
2024
Shandong University
2023
East China University of Science and Technology
2020-2022
Applied Radar (United States)
2022
Modification of target molecules by ubiquitin or ubiquitin-like (Ubl) proteins is generally reversible. Little known, however, about the physiological function reverse reaction, deconjugation. Atg8 a unique Ubl protein whose conjugation lipid phosphatidylethanolamine (PE). functions in formation double-membrane autophagosomes, central step well-conserved intracellular degradation pathway macroautophagy (hereafter autophagy). Here we show that deconjugation Atg8−PE cysteine protease Atg4...
The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments fight COVID-19. Current vaccine candidates use inactivated viruses; therefore, it is important understand architecture SARS-CoV-2. We have genetically structurally characterized β-propiolactone-inactivated viruses a propagated purified clinical strain observed that virus particles...
Since the outbreak of SARS-CoV-2 pandemic, there have been intense structural studies on purified viral components and inactivated viruses. However, ultrastructural evidence how infection progresses in native cellular context is scarce, a lack comprehensive knowledge replicative cycle. To correlate cytopathic events induced by with virus replication processes frozen-hydrated cells, we established unique multi-modal, multi-scale cryo-correlative platform to image Vero cells. This combines...
Coronaviruses remodel the intracellular host membranes during replication, forming double-membrane vesicles (DMVs) to accommodate viral RNA synthesis and modifications
Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development plasticity, ranging from axon guidance neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization, but extracellular regulation activation mechanisms remain unclear. Here we present crystal structures (PlxnA1, PlxnA2, PlxnA4) full ectodomains. Domains 1–9 form a ring-like conformation which the C-terminal 10 points away. All our ectodomain...
How thylakoid membranes are generated to form a metabolically active membrane network and how orchestrate the insertion localization of protein complexes for efficient electron flux remain elusive. Here, we develop method modulate biogenesis in rod-shaped cyanobacterium Synechococcus elongatus PCC 7942 by modulating light intensity during cell growth, probe spatial-temporal stepwise process cells. Our results reveal that plasma regularly arranged concentric layers have no physical...
Carboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. They encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) carbonic anhydrase catalyzing carbon fixation inside proteinaceous shell. How Rubisco complexes pack within the carboxysomes is unknown. Using cryo-electron tomography, we determine distinct 3D organization two distant α-carboxysomes from marine α-cyanobacterium Cyanobium sp. PCC 7001 where Rubiscos organized three...
Abstract Carboxysomes are a paradigm of self-assembling proteinaceous organelles found in nature, offering compartmentalisation enzymes and pathways to enhance carbon fixation. In α-carboxysomes, the disordered linker protein CsoS2 plays an essential role carboxysome assembly Rubisco encapsulation. Its mechanism action, however, is not fully understood. Here we synthetically engineer α-carboxysome shells using minimal shell components determine cryoEM structures these decipher principle The...
Background. In recent decades, the GII.4 norovirus genotype has predominated in epidemics worldwide and been associated with an increased rate of evolutionary change. 2014, a novel GII.17 variant emerged persisted, causing large outbreaks gastroenteritis China sporadic infections globally. The origin, evolution, transmission history this new are largely unknown. Methods. We generated 103 full capsid 8 whole-genome sequences strains collected between August 2013 November 2015 Guangdong,...
Bactericidal perforin-2 assembles an inactivated pre-pore complex and undergoes a 180° reconfiguration for membrane attack.
High-resolution cryoET structures of native HIV-1 capsid in complex with IP6 and CypA are enabled by viral membrane perforation.
Methane-oxidizing bacteria play a central role in greenhouse gas mitigation and have potential applications biomanufacturing. Their primary metabolic enzyme, particulate methane monooxygenase (pMMO), is housed copper-induced intracytoplasmic membranes (ICMs), of which the function biogenesis are not known. We show by serial cryo-focused ion beam (cryoFIB) milling/scanning electron microscope (SEM) volume imaging lamellae-based cellular cryo-electron tomography (cryoET) that these ICMs...
Abstract We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]‐spiroketals in high efficiency with generally diastereo‐ and enantioselectivities (up >20 : 1 dr, >99 % ee). In this procedure, readily available o ‐alkynylacetophenones undergo cycloisomerization generate isochromenes situ that participate stereoselective allylation/spiroketalization sequence 2‐(1‐hydroxyallyl)phenols. Meanwhile, 2‐(1‐hydroxyallyl)anilines were also compatible...
Kindlins co-activate integrins alongside talin. They possess, like talin, a FERM domain (4.1-erythrin–radixin–moiesin domain) comprising F0–F3 subdomains, but with pleckstrin homology (PH) inserted in the F2 subdomain that enables membrane association. We present crystal structure of murine kindlin-3 PH determined at resolution 2.23 Å and characterise its lipid binding using biophysical computational approaches. Molecular dynamics simulations suggest flexibility loops connecting β-strands...
Abstract Coxsackievirus A10 (CV-A10) is responsible for an escalating number of severe infections in children, but no prophylactics or therapeutics are currently available. KREMEN1 (KRM1) the entry receptor largest receptor-group hand-foot-and-mouth disease causing viruses, which includes CV-A10. We report here structures CV-A10 mature virus alone and complex with KRM1 as well A-particle. The spans viral canyon a large footprint on surface. has some overlap that seen neonatal Fc complexed...
An unprecedented iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides is reported. The ability acid promoter zinc triflate to perform multiple roles the key factor for success this strategy. This method provides scalable and efficient access biologically important azepino[3,4,5-cd] indoles in good yields generally excellent diastereo- enantioselectivities (up >20:1 dr >99% ee). Mild reaction conditions, easily accessible substrates...
Abstract Owing to their adjustable redox‐active sites, designable structures high porosity, and fully activated organic ligands, pristine metal‐organic frameworks (MOFs) have been widely utilized as advanced electrode materials (i. e., both anodes cathodes) for sodium‐ion batteries (SIBs) satisfied the insertion/extraction larger size mass of Na + cations, achieving significant progresses with excellent electrochemical performance in energy storage devices. Here, recent advances on MOFs...
Abstract Perforin-2 (PFN2, MPEG1) is a pore-forming protein that acts as first line of defense in the mammalian immune system, rapidly killing engulfed microbes within phagolysosome macrophages. PFN2 self-assembles into hexadecameric pre-pore rings transition upon acidification pores damaging target cell membranes. Here, using high-speed atomic force microscopy (HS-AFM) imaging and line-scanning molecular dynamics simulation, we elucidate to pore pathways dynamics. Upon acidification,...
Highlights•Subtomogram averaging of ChAdOx1 nCoV-19 spikes in situ at subnanometer resolution•HexaPro stabilizes the one-RBD-up prefusion spike conformation•In cryo-ET structure antigens provides rationale for vaccine optimizationSummaryVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven to be an effective means decreasing COVID-19 mortality, hospitalization rates, and transmission. One vaccines deployed worldwide is nCoV-19, which uses adenovirus...
There are only eight approved small molecule antiviral drugs for treating COVID-19. Among them, four nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, simnotrelvir-ritonavir). Antiviral resistance, unfavourable drug‒drug interaction, toxicity have been reported in previous studies. Thus there is a dearth of new treatment options SARS-CoV-2. In this work, three-tier cell-based screening was...
Diabetes is an extremely costly disease, one-third of which are attributed to the management diabetic foot disease including chronic, non-healing, ulcers (DFUs). Therefore, much effort needed understand pathogenesis DFUs and novel therapeutics. We utilized exosome staining confirm interaction between fibroblast-derived exosomes macrophages. Subsequently, we employed public data qPCR screen for upregulated miRNAs in DFUs. The relationship was validate miR-93-5 ATG16L1 through prediction...
Purpose: KLK7, also known as Kallikrein 7, is a secreted enzyme classified serine protease. Earlier studies have indicated that KLK10, and KLK11 are linked to the survival rates immune reactions of individuals with papillary thyroid cancer (PTC). This research examines investigating its role expression, evaluates viability treatment target for PTC. Methods: Initially, we examined expression possible functions KLK7 in PTC using bioinformatics techniques. Researchers impact on characteristics...
Delayed diabetic wound (DBW) healing is a severe complication of diabetes, characterized notably by peripheral sensory neuropathy. The underlying mechanism nerves and DBW remain unclear. Here, we demonstrate the role calcitonin gene-related peptide (CGRP) in regulating epithelialization angiogenesis DBW. Subsequently, design synthesis gelatin methacryloyl (GelMA-CGRP) hydrogel that slowly releases CGRP, evaluated its effect on promoting healing. results show CGRP abnormally downregulated...