A5045611603- Enzyme Structure and Function
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Biochemical Acid Research Studies
- Escherichia coli research studies
- Viral Infectious Diseases and Gene Expression in Insects
- Rheology and Fluid Dynamics Studies
- Glycosylation and Glycoproteins Research
- Metabolism and Genetic Disorders
- Mass Spectrometry Techniques and Applications
- Clostridium difficile and Clostridium perfringens research
- RNA and protein synthesis mechanisms
- Antimicrobial Resistance in Staphylococcus
- Amino Acid Enzymes and Metabolism
- Streptococcal Infections and Treatments
- Cell Adhesion Molecules Research
- Hippo pathway signaling and YAP/TAZ
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Blood properties and coagulation
- Parasites and Host Interactions
- Biochemical and Molecular Research
University of Glasgow
2014-2024
Institute of Infection and Immunity
2024
Beihang University
2011
Institut Laue-Langevin
2011
University of Leicester
1994-2007
University of Nottingham
1990-1999
University of Edinburgh
1997
Membrane traffic between the endoplasmic reticulum (ER) and Golgi apparatus through is a highly regulated process controlled by members of rab GTPase family. The GTP form rab1 regulates ER to transport interaction with vesicle tethering factor p115 cis-Golgi matrix protein GM130, also part complex GRASP65 important for organization cisternae. Here, we find that novel coiled-coil golgin-45 interacts medial-Golgi GRASP55 rab2 but not other proteins. Depletion disrupts causes block in secretory...
Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules their complexes, reporting on size shape in free solution. The purpose this multi-laboratory study was establish the precision accuracy basic data dimensions AUC validate previously proposed calibration techniques. Three kits cell assemblies containing radial temperature tools bovine serum albumin (BSA) reference sample were...
A class of anti-virulence compounds, the salicylidene acylhydrazides, has been widely reported to block function type three secretion system several Gram-negative pathogens by a previously unknown mechanism. In this work we provide first identification bacterial proteins that are targeted group compounds. We evidence their mode action is likely result from synergistic effect arising perturbation conserved proteins. also examine contribution selected target pathogenicity Yersinia...
Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, novel member this family from Pseudomonas aeruginosa, targets susceptible strains species through recognition the common polysaccharide antigen (CPA) P. aeruginosa lipopolysaccharide is predominantly homopolymer d-rhamnose. Structural biophysical analyses CPA occurs C-terminal carbohydrate-binding domain L1 interaction prerequisite for...
Mammalian pyruvate dehydrogenase multienzyme complex (PDC) is a key metabolic assembly comprising 60-meric pentagonal dodecahedral E2 (dihydrolipoamide acetyltransferase) core attached to which are 30 decarboxylase E1 heterotetramers and 6 dihydrolipoamide E3 homodimers at maximal occupancy. Stable integration mediated by an accessory E3-binding protein (E3BP) located on each of the 12 icosahedral faces. Here, we present evidence for novel subunit organization in E3BP form subcomplexes with...
Classical studies have focused on the role that individual regulators play in controlling virulence gene expression. An emerging theme, however, is bacterial metabolism also plays a key this process. Our previous work identified series of proteins were implicated regulation virulence. One these was AdhE, bi-functional acetaldehyde-CoA dehydrogenase and alcohol dehydrogenase. Deletion its (adhE) resulted elevated levels extracellular acetate stark pleiotropic phenotype: strong suppression...
Abstract Aldehyde-alcohol dehydrogenase (AdhE) is a key enzyme in bacterial fermentation, converting acetyl-CoA to ethanol, via two consecutive catalytic reactions. Here, we present 3.5 Å resolution cryo-EM structure of full-length AdhE revealing high-order spirosome architecture. The shows that the aldehyde (ALDH) and alcohol (ADH) active sites reside at outer surface inner respectively, thus topologically separating these activities. Furthermore, mutations disrupting helical abrogate...
Increasing rates of antibiotic resistance among Gram-negative pathogens such as Pseudomonas aeruginosa means alternative approaches to development are urgently required. Pyocins, produced by P. for intraspecies competition, highly potent protein antibiotics known actively translocate across the outer membrane aeruginosa. Understanding and exploiting mechanisms which pyocins target, penetrate kill is a promising approach development. In this work we show therapeutic potential newly identified...
The PDZ domain, also known as the GLGF repeat/DHR is an ∼90-amino acid motif discovered in a recently identified family of proteins termed MAGUKs (membrane-associated guanylatekinase homologues). Sequence comparison analysis has since domains over 50 proteins. Like SH2 and SH3 domains, mediate specific protein-protein interactions, whose specificities appear to be dictated by primary structure domain well its binding target. Using recombinant fusion blot overlay assay, we show that single...
Type I DNA restriction/modification enzymes protect the bacterial cell from viral infection by cleaving foreign which lacks N6-adenine methylation within a target sequence and maintaining of targets on host chromosome. It has been noted that genes specifying type systems can be transferred to new lacking appropriate, protective without any adverse effect. The modification phenotype apparently appears before restriction phenotype, but no evidence for transcriptional or translational control...
Mammalian pyruvate dehydrogenase complex (PDC) is a key multi-enzyme assembly that responsible for glucose homeostasis maintenance and conversion of into acetyl-CoA. It comprises central pentagonal dodecahedral core consisting two subunit types (E2 E3BP) to which peripheral enzymes (E1 E3) bind tightly but non-covalently. Currently, there are conflicting models PDC (E2+E3BP) organisation: the 'addition' model (60+12) 'substitution' (48+12). Here we present first ever low-resolution...
Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival or eukaryotic cells. However, mechanism of T6SS is incompletely understood. In present study, we investigated a conserved component T6SS, TssK, using antibacterial Serratia marcescens as model system. TssK was confirmed be essential for effector by T6SS. The native protein, although not an integral membrane appeared localize inner membrane, consistent with its presence within membrane-anchored...
Article5 March 2020Open Access Transparent process Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1 Bethan Medina-Pritchard orcid.org/0000-0002-6736-9203 Wellcome Centre Cell Biology, University of Edinburgh, UK Search more papers this author Vasiliki Lazou Juan Zou Olwyn Byron School Life Sciences, Glasgow, Maria A Abad Juri Rappsilber orcid.org/0000-0001-5999-1310 Institute Biotechnology, Technische Universität Berlin, Germany Patrick Heun Arockia Jeyaprakash...
Pneumolysin is a member of the family related bacterial thiol-activated toxins, which share structural similarities and proposed common cytolytic mechanism.Currently molecular mechanism membrane damage caused by these toxins remains matter controversy.Aprerequisite for defining this detailed knowledge monomeric oligomeric pneumolysin structures.W e present first time details structure toxin, pneumolysin.Electron microscope images metal-shadowed monomers show an asymmetric molecule composed...
Abstract Iron is a limiting nutrient in bacterial infection putting it at the centre of an evolutionary arms race between host and pathogen. Gram-negative bacteria utilize TonB-dependent outer membrane receptors to obtain iron during infection. These acquire either concert with soluble iron-scavenging siderophores or through direct interaction extraction from proteins. Characterization these provides invaluable insight into pathogenesis. However, only subset virulence-related have been...
Abstract Aldehyde-alcohol dehydrogenase (AdhE) is an enzyme responsible for converting acetyl-CoA to ethanol via acetaldehyde using NADH. AdhE composed of two catalytic domains aldehyde (ALDH) and alcohol (ADH), forms a spirosome architecture critical activity. Here, we present the atomic resolution (3.43 Å) cryo-EM structure spirosomes in extended conformation. The shows that undergo structural transition from compact forms, which may result cofactor binding. This leads access substrate...