A5003402066- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- Bacterial Genetics and Biotechnology
- Metabolomics and Mass Spectrometry Studies
- Lipid Membrane Structure and Behavior
- Analytical Chemistry and Chromatography
- Heat shock proteins research
- Photosynthetic Processes and Mechanisms
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Antibiotic Resistance in Bacteria
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Ion-surface interactions and analysis
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Drug Transport and Resistance Mechanisms
- Microtubule and mitosis dynamics
University of Oxford
2016-2025
Maastricht University
2024
Indiana University School of Medicine
2024
University of Newcastle Australia
2023
The University of Adelaide
2023
Oxford Research Group
2011-2021
Kavli Energy NanoScience Institute
2021
Science Oxford
2017-2020
Oxfam
2015-2018
Oxford Technologies (United Kingdom)
2018
Interpretation of mass spectra is challenging because they report a ratio two physical quantities, and charge, which may each have multiple components that overlap in m/z. Previous approaches to disentangling the focused on peak assignment or fitting. However, former struggle with complex spectra, latter are generally computationally intensive require substantial manual intervention. We propose new data analysis approach employs Bayesian framework separate charge dimensions. On basis this...
Under solution conditions where the native state is destabilized, largely helical polypeptide hormone insulin readily aggregates to form amyloid fibrils with a characteristic cross-β structure. However, there lack of information relating 4.8 Å β-strand repeat higher order assembly fibrils. We have used cryo-electron microscopy (EM), combining single particle analysis and reconstruction, characterize these study three-dimensional (3D) arrangement their component protofilaments. Low-resolution...
Collision cross sections in both helium and nitrogen gases were measured directly using a drift cell with RF ion confinement inserted within quadrupole/ion mobility/time-of-flight hybrid mass spectrometer (Waters Synapt HDMS, Manchester, U.K.). for large set of denatured peptide, protein, native-like protein complex ions are reported here, forming database collision that spans over 2 orders magnitude. The average effective density the is 0.6 g cm(-3), which significantly lower than...
We have examined the architecture of a protein complex in absence bulk water. By determining collision cross sections assemblies trp RNA binding protein, TRAP, we established that 11-membered ring topology can be maintained within mass spectrometer. also found tryptophan enhances stability structure and addition specific molecule increases size prevents structural collapse. These results provide definitive evidence quaternary water highlight potential ion mobility separation for defining...
Hydrogen-deuterium exchange measurements are becoming increasingly important in studies of the dynamics protein molecules and, particularly, their folding behavior. Electrospray ionization mass spectrometry (ESI-MS) has been used to obtain distribution masses within a population that had undergone hydrogen solution. This information is complementary from nuclear magnetic resonance spectroscopy (NMR) experiments, which measure average occupancy individual sites over molecules. In experiments...
We report the design and first applications of a tandem mass spectrometer (a quadrupole time-of-flight spectrometer) optimized for transmission analysis large macromolecular assemblies. Careful control pressure gradient in different pumping stages instrument has been found to be essential detection particles. Such assemblies are, however, difficult analyze by tandem-MS approaches, because they give rise signals above m/z 3,000-4,000, limit commercial quadrupoles. By reducing frequency 300...
Abstract Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and electron microscopy (EM) have been used simultaneously to follow the temperature‐induced formation of amyloid fibrils by bovine insulin at acidic pH. The FTIR CD data confirm that, before heating, molecules in solution pH 2.3 a predominantly native‐like α‐helical structure. On heating 70°C, partial unfolding occurs results initially aggregates that are shown FT‐IR spectra retain helical Following this step,...
Dynactin is an essential cofactor for the microtubule motor cytoplasmic dynein-1. We report structure of 23-subunit dynactin complex by cryo-electron microscopy to 4.0 angstroms. Our reconstruction reveals how built around a filament containing eight copies actin-related protein Arp1 and one β-actin. The capped at each end distinct complexes, its length defined elongated peptides that emerge from α-helical shoulder domain. A further 8.2 angstrom between dynein, dynactin, motility-inducing...
Targeted gene silencing by RNAi requires the RNA-induced complex (RISC), whose core component is protein Argonaute (Ago) bound to a microRNA (miRNA) or an siRNA. In humans, Ago2 loaded with miRNAs action of specialized assembly called RISC-loading (RLC), comprising proteins Ago2, Dicer, and TRBP. Here we show that human RLC assembles spontaneously in vitro from purified components. No cofactors chaperones are required for form. The reconstituted RLC, containing one copy each protein, has...
The seven members of the human 14-3-3 protein family regulate a diverse range cell signaling pathways by formation protein-protein complexes with proteins that contain phosphorylated Ser/Thr residues within specific sequence motifs. Previously, crystal structures three isoforms (zeta, sigma, and tau) have been reported, structural data for two deposited in Protein Data Bank (zeta sigma). In this study, we provide detail five bound to ligands, providing coverage all family. A comparative...
We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering m/z range 122.1-609.3, nitrogen collision cross-section (Ω(N(2))) 124.5-254.3 Å(2) and helium (Ω(He)) 63.0-178.8 Å(2). Absolute Ω(N(2)) Ω(He) values for calibrants two diastereomers were measured using drift-tube instrument with radio frequency (RF) confinement. T-wave drift-times protonated betamethasone dexamethasone are reproducibly different. Calibration these yields...
Class I histone deacetylases (HDAC1, HDAC2, and HDAC3) are recruited by cognate corepressor proteins into specific transcriptional repression complexes that target HDAC activity to chromatin resulting in condensation silencing. We previously reported the structure of HDAC3 complex with SMRT corepressor. This revealed presence inositol-tetraphosphate [Ins(1,4,5,6)P4] at interface two proteins. It was unclear whether role Ins(1,4,5,6)P4 is act as a structural cofactor or regulator activity....