A5091006983- Protein Structure and Dynamics
- Alzheimer's disease research and treatments
- Advanced NMR Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- NMR spectroscopy and applications
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Metabolomics and Mass Spectrometry Studies
- Prion Diseases and Protein Misfolding
- Advanced Biosensing Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- Chemical Synthesis and Analysis
- Electron Spin Resonance Studies
- Plasmonic and Surface Plasmon Research
- Spectroscopy and Quantum Chemical Studies
- RNA modifications and cancer
- Advanced Materials and Mechanics
- Science and Climate Studies
- Advanced Glycation End Products research
- Allergic Rhinitis and Sensitization
- Lanthanide and Transition Metal Complexes
- Blood properties and coagulation
- Viral Infectious Diseases and Gene Expression in Insects
- Amyloidosis: Diagnosis, Treatment, Outcomes
Avacta (United Kingdom)
2017
Manchester Airport
2013
University of Leeds
2004-2011
Massachusetts Institute of Technology
2010
Institute of Structural and Molecular Biology
2009
University of Nottingham
2001-2005
Queen's Medical Centre
2003
Molecular recognition reagents are key tools for understanding biological processes and used universally by scientists to study protein expression, localisation interactions. Antibodies remain the most widely of such many show excellent performance, although some poorly characterised or have stability batch variability issues, supporting use alternative binding proteins as complementary applications. Here we report on Affimer research reagents. We selected 12 diverse molecular targets...
The structure adopted by biomaterials, such as proteins, at interfaces is a crucial parameter in range of important biological problems. It critical property defining the functionality cell/bacterial membranes and biofilms (i.e., antibiotic-resistant infections) exploitation immobilized enzymes biocatalysis. intrinsically small quantities materials precludes application conventional spectroscopic phenomena routinely used for (bio)structural analysis due to lack sensitivity. We show that...
Amyloid is a highly ordered form of aggregate comprising long, straight and unbranched proteinaceous fibrils that are formed with characteristic nucleation-dependent kinetics in vitro. Currently, the structural molecular mechanism fibril nucleation elongation poorly understood. Here, we investigate role sequence structure initial monomeric precursor determining rates human beta(2)-microglobulin (beta(2)m). We describe seeded spontaneous (unseeded) growth wild-type beta(2)m 12 variants at pH...
β2-Microglobulin (β2m) is the major structural component of amyloid fibrils deposited in a condition known as dialysis-related amyloidosis. Despite numerous studies that have elucidated important aspects fibril formation process vitro, and magic angle spinning (MAS) NMR study formed by small peptide fragment, details β2m full-length 99-residue protein are largely unknown. Here, we present site-specific MAS analysis compare spectra prepared under two different conditions. Specifically, long...
Despite much progress in understanding the folding and aggregation processes of proteins, rules defining their interplay have yet to be fully defined. This problem is particular importance since many diseases are initiated by protein unfolding hence propensity aggregate competes with intramolecular collapse other events. Here, we describe roles intermolecular interactions length lag time apparent rate elongation 100-residue human beta(2)-microglobulin at pH 2.5, commencing from an...
The deposition of amyloid-like fibrils, composed primarily the 99-residue protein β2-microglobulin (β2m), is one characteristic symptoms dialysis-related amyloidosis. Fibrils formed in vitro at low pH and salt concentration share many properties with disease related fibrils have been extensively studied by a number biochemical biophysical methods. These contain significant β-sheet core complex cryoEM electron density profile. Here, we investigate intrasheet arrangement means 15N−13C MAS NMR...
The analytical characterization of biopharmaceuticals is a fundamental step in the early stages development and prediction their behavior bioprocesses. Protein aggregation particular common issue as it affects all product development. In present work, we investigate stability kinetics A33Fab, therapeutically relevant humanized antibody fragment at wide range pH, ionic strength, temperature. We show that propensity A33Fab to aggregate under thermally accelerated conditions pH ionic-strength...
beta(2)-microglobulin (beta(2)m) is a 99-residue protein with an immunoglobulin fold that forms beta-sheet-rich amyloid fibrils in dialysis-related amyloidosis. Here the environment and accessibility of side chains within formed vitro from beta(2)m long straight morphology are probed by site-directed spin labeling to modification N-ethyl maleimide using 19 site-specific cysteine variants. Continuous wave electron paramagnetic resonance spectroscopy these reveals core predominantly organized...
A F45W mutant of yeast ubiquitin has been used as a model system to examine the effects nonnative local interactions on protein folding and stability. Mutating native TLTGK G-bulged type I turn in N-terminal β-hairpin NPDG stabilizes β-strand alignment isolated peptide fragment. However, NMR structural analysis proteins shows that is forced adopt an unfavorable turn. The significantly less stable (∼9 kJ mol-1) folds 30 times slower than sequence, demonstrating can modulate stability...
We describe the design and characterisation of two simple 'metalloproteins' based on Zn2+ co-ordination sites involving histidine residues close to N- C-termini β-hairpin peptides (His2-β, KHYTVSINGKKITVHI His3-β, HKHYTV-SINGKKITVHI); we show by NMR circular dichroism spectroscopy that complexation co-operatively enhances stability these partially pre-organised β-sheet peptides.
Substitution of trans ‐proline at three positions in ubiquitin (residues 19, 37 and 38) produces significant context‐dependent effects on protein stability (both stabilizing destabilizing) that reflect changes to a combination parameters including backbone flexibility, hydrophobic interactions, solvent accessibility polar groups intrinsic conformational preferences. Kinetic analysis the wild‐type yeast reveals predominant fast‐folding phase which conforms an apparent two‐state folding model....
Twist and shout: Dynamics within amyloid fibrils are probed using solution NMR spectroscopy (see 1H–15N HSQC spectra of wild-type β2-microglobulin a variant with an extended N-terminal region). A novel method is employed to ensure the origin signals take molecular recycling from into account. Detailed facts importance specialist readers published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note:...
Back to the fold: A new method determining stability of a β hairpin is described. forming sequence (β4) introduced into native ubiquitin (see structure) enabling contribution protein this structural motif be estimated. This data provides both an upper limit on for autonomously folding hairpins, and spectroscopic reference state estimating related peptides in solution.
Twist and shout: Die Dynamik von Amyloidfibrillen wird mit Lösungs-NMR-Spektroskopie analysiert (siehe 1H-15N-HSQC-NMR-Spektren Wildtyp-β2-Mikroglobulin und einer Variante verlängerter N-terminaler Region). Ein neuartiges Verfahren angewendet, das die Herkunft der NMR-Signale sicherstellt Molekülrecycling Fibrillen berücksichtigt.