A5030676931- Enzyme Structure and Function
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Viral gastroenteritis research and epidemiology
- Animal Disease Management and Epidemiology
- Glycosylation and Glycoproteins Research
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Monoclonal and Polyclonal Antibodies Research
- DNA and Nucleic Acid Chemistry
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
- Cancer Research and Treatments
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Vector-Borne Animal Diseases
- Viral Infections and Immunology Research
- Enzyme Production and Characterization
- Viral Infectious Diseases and Gene Expression in Insects
- Hepatitis C virus research
- Trace Elements in Health
- Advanced Electron Microscopy Techniques and Applications
Diamond Light Source
2016-2025
University of Oxford
2011-2024
Centre for Human Genetics
2010-2024
Research Complex at Harwell
2016-2024
Rutherford Appleton Laboratory
2017-2024
École Normale Supérieure de Lyon
2023
Institut de génétique et de biologie moléculaire et cellulaire
2017
Šiauliai University
2013
Institute for Molecular Medicine Finland
2013
University of Helsinki
2013
Significance Synthetic polymers are ubiquitous in the modern world but pose a global environmental problem. While plastics such as poly(ethylene terephthalate) (PET) highly versatile, their resistance to natural degradation presents serious, growing risk fauna and flora, particularly marine environments. Here, we have characterized 3D structure of newly discovered enzyme that can digest crystalline PET, primary material used manufacture single-use plastic beverage bottles, some clothing,...
Abstract The ribosome, the largest RNA-containing macromolecular machinery in cells, requires metal ions not only to maintain its three-dimensional fold but also perform protein synthesis. Despite vast biochemical data regarding importance of for efficient synthesis and increasing number ribosome structures solved by X-ray crystallography or cryo-electron microscopy, assignment within remains elusive due methodological limitations. Here we present extensive experimental on potassium...
Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only glycoprotein, E, whereas pestiviruses hepacivirus encode two glycoproteins, E1 E2. Although E2 is involved in attachment, it has been unclear which protein responsible for We report crystal structures homodimeric from pestivirus bovine...
Influenza virus polymerase transcribes or replicates the segmented RNA genome (vRNA) into respectively viral mRNA full-length copies and initiates synthesis by binding conserved 3′ 5′ vRNA ends (the promoter). In recent structures of promoter-bound polymerase, cap-binding endonuclease domains are configured for cap snatching, which generates capped transcription primers. Here, we present a FluB structure with bound complementary cRNA end that exhibits major rearrangement subdomains within...
This first structure of the enzyme converting dopamine to norepinephrine provides new perspectives on numerous disorders.
Abstract Many bacteria and archaea possess a two-dimensional protein array, or S-layer, that covers the cell surface plays crucial roles in physiology. Here, we report crystal structure of SlpA, main S-layer bacterial pathogen Clostridioides difficile , use electron microscopy to study organisation assembly. The SlpA lattice mimics assembly cell, through tiling triangular prisms above wall, interlocked by distinct ridges facing environment. Strikingly, array is very compact, with pores only...
Abstract Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with matrix components. Semaphorin-5A (Sema5A) a bifunctional cue exerting attractive inhibitory effects neuronal growth through the interaction heparan sulfate (HS) chondroitin (CS) glycosaminoglycans (GAGs), respectively. Sema5A harbors seven thrombospondin type-1 repeats (TSR1-7) important GAG binding, however...
The enterobacterial common antigen (ECA) is conserved in Gram-negative bacteria of the Enterobacterales order although its function debated. ECA biogenesis depends on Wzx/Wzy-dependent strategy whereby newly synthesized lipid-linked repeat units, lipid III, are transferred across inner membrane by III flippase WzxE. WzxE part Wzx family and required many glycan assembly systems, but an understanding molecular mechanism hindered due to a lack structural evidence. Here, we present first X-ray...
We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, presacral mass, renal and palatal agenesis, pulmonary hypoplasia. It results from C470R in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5(Vcc/null)) completely recapitulate Pcsk5(Vcc/Vcc) phenotype, as does epiblast-specific conditional...
Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, conserved proteins pUL31 and pUL34 form heterodimeric egress complex (NEC), which, in turn, mediates formation of tight-fitting membrane vesicles around at inner membrane. Here, we present crystal structure pseudorabies virus NEC. The revealed that zinc finger motif an extensive interaction network between two stabilize...
Hepatitis C virus (HCV) infection remains a major health problem worldwide. HCV entry into host cells and membrane fusion are achieved by two envelope glycoproteins, E1 E2. We report here the 3.5-Å resolution crystal structure of N-terminal domain ectodomain, which reveals complex network covalently linked intertwined homodimers that do not harbour expected truncated class II protein fold.
Article1 September 2017Open Access Source DataTransparent process Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD Kiran Bountra Department of Life Sciences, Imperial College London, UK Rutherford Appleton Laboratory, Research Complex at Harwell, Oxfordshire, Search more papers this author Gregor Hagelueken Institute Physical and Theoretical Chemistry, University Bonn, Germany Hassanul G Choudhury Valentina Corradi Centre Molecular Simulation...
Abstract Termination of RNA polymerase II (Pol II) transcription is an important step in the cycle, which involves dislodgement from DNA, leading to release a functional transcript. Recent studies have identified key players required for this process and showed that common feature these proteins conserved domain interacts with phosphorylated C-terminus Pol (CTD-interacting domain, CID). However, mechanism by termination achieved not understood. Using genome-wide methods, here we show fission...
The insulin-linked polymorphic region is a variable number of tandem repeats DNA in the promoter insulin gene that regulates transcription insulin. This known to form alternative structures, i-motifs and G-quadruplexes. Individuals have different sequence variants although previous work investigated effects some on G-quadruplex formation, there not clear picture relationship between diversity, structures formed, functional expression. Here we show linked vitro. Additionally, reporter genes...
Cell fate is governed by combinatorial actions of transcriptional regulators assembling into multiprotein complexes. However, the molecular details how these complexes form are poorly understood. One such complex, which contains basic-helix-loop-helix heterodimer SCL:E47 and bridging proteins LMO2:LDB1, critically regulates hematopoiesis induces T cell leukemia. Here, we report crystal structure (SCL:E47)bHLH:LMO2:LDB1LID bound to DNA, providing a account network interactions this complex....
Potassium ion channels utilize a highly selective filter to rapidly transport K+ ions across cellular membranes. This selectivity is composed of four binding sites which display almost equal electron density in crystal structures with high potassium concentrations. can be interpreted reflect superposition alternating and water occupied states or as adjacent ions. Here, we use single wavelength anomalous dispersion (SAD) X-ray diffraction data collected near the absorption edge show...
The Salmonella-secreted effector SseK3 translocates into host cells, targeting innate immune responses, including NF-κB activation. is a glycosyltransferase that transfers an N-acetylglucosamine (GlcNAc) moiety onto the guanidino group of target arginine, modulating cell function. However, lack structural information has precluded elucidation molecular mechanisms in arginine and GlcNAc selection. We report here crystal structure its apo form complex with hydrolyzed UDP-GlcNAc. possesses...
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of most widespread tick-borne viral infection in humans. CCHFV encodes a secreted glycoprotein (GP38) unknown function that target protective antibody. Here, we present crystal structure GP38 at resolution 2.5 Å, which revealed novel fold primarily consisting 3-helix bundle and β-sandwich. Sequence alignment homology modeling showed distant between ectodomain Gn (a structural CCHFV), suggestive gene duplication event....
Abstract Neutrophils play essential anti-microbial and inflammatory roles in host defense, however, their activities require tight regulation as dysfunction often leads to detrimental autoimmune diseases. Here we show that the adhesion molecule GPR97 allosterically activates CD177-associated membrane proteinase 3 (mPR3), conjugation with several protein interaction partners neutrophil activation humans. Crystallographic deletion analysis of extracellular region identified two independent...