A5014650241- Alzheimer's disease research and treatments
- Drug Transport and Resistance Mechanisms
- Trace Elements in Health
- Genomics and Chromatin Dynamics
- Biochemical effects in animals
- Microtubule and mitosis dynamics
- Protein Structure and Dynamics
- Metal complexes synthesis and properties
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Photoreceptor and optogenetics research
- Free Radicals and Antioxidants
- RNA Research and Splicing
- Spaceflight effects on biology
- Advanced biosensing and bioanalysis techniques
- Herpesvirus Infections and Treatments
- Cellular Mechanics and Interactions
- Photosynthetic Processes and Mechanisms
- Insect and Pesticide Research
- CRISPR and Genetic Engineering
- Molecular Sensors and Ion Detection
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
Imperial College London
2014-2025
MRC London Institute of Medical Sciences
2021
Lung Institute
2019
Abstract The kinetics of the interactions between amyloid‐β (Aβ) and metal ions are crucial to understanding physiological pathological roles Aβ in normal brain Alzheimer’s disease. Using quenching a fluorescent probe by Cu 2+ , mechanism Aβ/Cu physiologically relevant conditions has been elucidated. binds at near diffusion‐limited rate, initially forming component I. switching I II occurs on second timescale, with significant energy barrier. Component is much more reactive towards ligands...
Tetramethylrhodamine (TMR) is a fluorescent dye whose self-quenching has been used as probe of multiple biological phenomena. We determine the distance-dependence and place bounds on timescale TMR dissociation. Our results validate fluorescence an alternative to FRET enable future assays be designed with confidence.
The yeast SWR1 complex catalyzes the exchange of histone H2A/H2B dimers in nucleosomes with Htz1/H2B dimers. We use cryoelectron microscopy to determine structure an enzyme-bound hexasome intermediate reaction pathway exchange, which dimer has been extracted from a nucleosome prior insertion comprising Htz1/H2B. reveals key role for Swc5 subunit stabilizing unwrapping DNA core hexasome. By engineering crosslink between and its chaperone protein Chz1, we show that this blocks by but allows...
N-Truncated Aβ4-42 displays a high binding affinity with CuII. A mechanistic scheme of the interactions between and CuII has been proposed using fluorescence approach. The timescales different conversion steps were determined. This kinetic mechanism indicates potential synaptic functions during neurotransmission.
Mutations and post-translational modifications of amyloid-β (Aβ) peptide in its N terminus have been shown to increase fibril formation, yet the molecular mechanism is not clear. Here we investigated kinetics interactions copper with two Aβ peptides containing Familial Alzheimer's disease (FAD) mutations (English (H6R) Tottori (D7N)), as well phosphorylated at serine 8 (pS8). All three bind a similar rate wild-type (wt). The dissociation rates follow order pS8>H6R>wt>D7N; interconversion...
Abstract The kinetics of the interactions between amyloid‐β (Aβ) and metal ions are crucial to understanding physiological pathological roles Aβ in normal brain Alzheimer’s disease. Using quenching a fluorescent probe by Cu 2+ , mechanism Aβ/Cu physiologically relevant conditions has been elucidated. binds at near diffusion‐limited rate, initially forming component I. switching I II occurs on second timescale, with significant energy barrier. Component is much more reactive towards ligands...
Homologous recombination (HR) factors are crucial for DSB repair and processing stalled replication forks. RAD51 paralogs, including RAD51B, RAD51C, RAD51D, XRCC2 XRCC3, have emerged as essential tumour suppressors, forming two subcomplexes, BCDX2 CX3. Mutations in these genes associated with cancer susceptibility Fanconi anaemia, yet their biochemical activities remain unclear. This study reveals a linear arrangement of subunits compared to the ring. shows strong affinity towards...
Abstract The yeast SWR1 complex catalyses the exchange of histone H2A–H2B dimers in nucleosomes, with Htz1–H2B 1–3 . Here we used single-molecule analysis to demonstrate two-step double two a canonical nucleosome dimers, and showed that can be processive without release from complex. Further bound nucleosomes flip between states, each presenting different face, hence dimer, SWR1. dwell time is longer when an dimer presented for than dimer. A hexasome intermediate reaction single orientation...
The ability of the amyloid-β peptide to bind redox active metals and act as a source radical damage in Alzheimer's disease has been largely accepted contributing disease's pathogenesis. However, kinetic understanding molecular mechanism, which underpins this generation, yet be reported. Here we use sensitive fluorescence approach, reports on oxidation state metal bound can therefore shed light kinetics. We confirm that goes via low populated, reactive intermediate reaction proceeds Component...
Structure-based drug design is commonly used to guide the development of potent and specific enzyme inhibitors. Many enzymes - such as protein kinases adopt multiple conformations, conformational interconversion expected impact on small molecule We measured dynamic equilibrium between DFG-in-like active DFG-out-like inactive conformations activation loop unphosphorylated Aurora-A alone, in presence activator TPX2, kinase The had a shorter residence time conformation shift position towards...
Tetramethylrhodamine (TMR) is a fluorescent dye whose self-quenching has been used as probe of multiple biological phenomena. We determine the distance-dependence TMR and place bounds on timescale dissociation. Our results validate fluorescence an alternative to FRET enable future assays be designed with confidence.
Abstract Herpesviruses are ubiquitous human pathogens, which the causative agent of mild to severe symptoms ranging from cold sore nasopharyngeal carcinoma. Even though replication linear dsDNA genome has been studied for decades, we still lack a complete molecular understanding its mechanism. It proposed, but never shown directly, that HSV-1 origin binding protein UL9 binds two closely located sites within oriS sequence, thereby mediating looping, in turn facilitates initiation. Here, used...