A5031154891- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Drug Transport and Resistance Mechanisms
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Vibrio bacteria research studies
- RNA modifications and cancer
- Analytical Chemistry and Chromatography
- Cystic Fibrosis Research Advances
- Metabolomics and Mass Spectrometry Studies
- Bacterial Genetics and Biotechnology
- Electron Spin Resonance Studies
- Amino Acid Enzymes and Metabolism
- Ubiquitin and proteasome pathways
- Chemical Reactions and Isotopes
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Microbial Metabolites in Food Biotechnology
- Polyamine Metabolism and Applications
- Microtubule and mitosis dynamics
- Force Microscopy Techniques and Applications
Université Libre de Bruxelles
2012-2024
Synchrotron soleil
2024
VIB-VUB Center for Structural Biology
2023
King's College London
2017-2021
King's College Hospital
2019
Abstract Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages 1–3 . Similar how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns 4 (PAMPs), many bacterial that respond bacteriophage infection require phage-specific triggers be activated. However, identities such and sensing remain largely unknown. Here we identify investigate anti-phage function CapRel SJ46 , a fused...
Abstract Secondary transporters undergo structural rearrangements to catalyze substrate translocation across the cell membrane – yet how such conformational changes happen within a lipid environment remains poorly understood. Here, we combine hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics (MD) simulations understand lipids regulate of secondary at level. Using homologous XylE, LacY and GlpT from Escherichia coli as model systems, discover that conserved...
Abstract The interplay between membrane proteins and the lipids of is important for cellular function, however, tools enabling interrogation protein dynamics within native lipid environments are scarce often invasive. We show that styrene–maleic acid particle (SMALP) technology can be coupled with hydrogen–deuterium exchange mass spectrometry (HDX‐MS) to investigate conformational bilayers. demonstrate changes in accessibility rhomboid protease GlpG, captured three different compositions,...
Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) additionally include SecB-like chaperone that stabilizes the antitoxin recognizing its addiction (ChAD) element. TACs mediate antiphage defense, but mechanisms viral sensing and restriction unexplored. We identify two Escherichia coli TAC containing host inhibition growth (HigBA) CmdTA TA modules, HigBAC CmdTAC. is triggered through recognition gpV major...
Hydrogen deuterium exchange-mass spectrometry (HDX-MS) has emerged as a powerful technique for interrogating the conformational dynamics of proteins and their complexes. Currently, analysis HDX-MS data remains laborious procedure, mainly due to lack streamlined software process large datasets. We present Deuteros which is standalone designed be coupled with Waters DynamX HDX software, allowing rapid visualization from differential HDX-MS.Deuteros open-source can downloaded...
Proton-coupled transporters use transmembrane proton gradients to power active transport of nutrients inside the cell. High-resolution structures often fail capture coupling between and ligand binding, conformational changes associated with transport. We combine HDX-MS mutagenesis MD simulations dissect molecular mechanism prototypical transporter XylE. show that protonation a conserved aspartate triggers transition from outward-facing inward-facing state. This only occurs in presence...
Abstract Acinetobacter baumannii is a nosocomial pathogen highly resistant to environmental changes and antimicrobial treatments. Regulation of cellular motility biofilm formation important for its virulence, although it poorly described at the molecular level. It has been previously reported that genus specifically produces small positively charged metabolite, polyamine 1,3-diaminopropane, associated with cell virulence. Here we show A. encodes novel acetyltransferase, Dpa, acetylates...
Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures the neddylated and deneddylated CSN-CRL2 complexes combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These suggest conserved mechanism CSN activation, consisting conformational clamping CRL2 CSN2/CSN4,...
Rel stringent factors are bifunctional ribosome-associated enzymes that catalyze both synthesis and hydrolysis of the alarmones (p)ppGpp. Besides allosteric control by starved ribosomes (p)ppGpp, is regulated various protein depending on specific stress conditions, including c-di-AMP-binding DarB. However, how these effector proteins remains unknown. We have determined crystal structure DarB2:RelNTD2 complex, uncovering DarB directly engages SYNTH domain to stimulate (p)ppGpp synthesis. This...
Eukaryotic innate immune systems use pattern recognition receptors to sense infection by detecting pathogen-associated molecular patterns, which then triggers an response. Bacteria have similarly evolved immunity proteins that certain components of their viral predators, known as bacteriophages
Eukaryotic innate immune systems use pattern recognition receptors (PRRs) to sense infection by detecting pathogen-associated molecular patterns, which then triggers an response. Bacteria have similarly evolved immunity proteins that certain components of their viral predators known as bacteriophages. Although different can recognize phage-encoded triggers, individual bacterial only been found a single trigger during infection, suggesting one-to-one relationship between PRRs and ligands....
Transporters cycle through large structural changes to translocate molecules across biological membranes. The temporal relationships between these and function, the molecular properties setting their rates, determine transport efficiency-yet remain mostly unknown. Using single-molecule fluorescence microscopy, we compare timing of conformational transitions substrate uptake in elevator-type transporter GltPh We show that elevator-like movements substrate-loaded domain membranes release are...
Bacteria have evolved sophisticated and diverse immunity mechanisms to protect themselves against a nearly constant onslaught of bacteriophages 1–3 . Similar how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns (PAMPs) 4 , many bacterial that respond bacteriophage infection require phage-specific trigger be activated. However, the identities such triggers mechanistic basis sensing remain almost completely unknown. Here, we discover...
Abstract The interplay between membrane proteins and the lipids of is important for cellular function, however, tools enabling interrogation protein dynamics within native lipid environments are scarce often invasive. We show that styrene–maleic acid particle (SMALP) technology can be coupled with hydrogen–deuterium exchange mass spectrometry (HDX‐MS) to investigate conformational bilayers. demonstrate changes in accessibility rhomboid protease GlpG, captured three different compositions,...
Proteins are an important class of biological macromolecules that play many key roles in cellular functions including gene expression, catalyzing metabolic reactions, DNA repair and replication. Therefore, a detailed understanding these processes provides critical information on how cells function. Integrative structural MS methods offer dynamical protein complex assembly, connectivity, subunit stoichiometry, oligomerization ligand binding. Recent advances integrative have allowed for the...
Summary Toxin-antitoxins (TAs) are prokaryotic two-gene systems comprised of a toxin neutralised by an antitoxin. Toxin-antitoxin-chaperone (TAC) additionally include SecB-like chaperone that stabilises the antitoxin recognising its addiction (ChAD) element. TACs have been shown to mediate antiphage defence, but mechanisms viral sensing and restriction unexplored. We identify characterise two Escherichia coli TAC containing HigBA CmdTA TA units, HigBAC CmdTAC. The is triggered through...