A5080455454- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Ion-surface interactions and analysis
- Metabolomics and Mass Spectrometry Studies
- Advanced X-ray Imaging Techniques
- Analytical Chemistry and Chromatography
- Advanced Proteomics Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- X-ray Spectroscopy and Fluorescence Analysis
- RNA and protein synthesis mechanisms
- Heat shock proteins research
- Diffusion and Search Dynamics
- ATP Synthase and ATPases Research
- Spectroscopy and Quantum Chemical Studies
- DNA and Nucleic Acid Chemistry
- Analytical chemistry methods development
- Mitochondrial Function and Pathology
- Electrohydrodynamics and Fluid Dynamics
- Viral gastroenteritis research and epidemiology
- RNA Research and Splicing
- Isotope Analysis in Ecology
- Animal Virus Infections Studies
- Cell Image Analysis Techniques
- Hemoglobin structure and function
Uppsala University
2013-2025
Science for Life Laboratory
2012-2020
University of Oxford
2014-2018
Lawrence Livermore National Laboratory
2007
Stanford Synchrotron Radiation Lightsource
2007
SLAC National Accelerator Laboratory
2007
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...
Watching proteins' weight Careful measurements of light scattering can provide information on individual macromolecules and complexes. Young et al. used a light-scattering approach for accurate mass determination proteins as small 20 kDa (see the Perspective by Lee Klenerman). Movies protein complex association dissociation were analyzed to extract biophysical parameters from single molecules assemblies without labeling. Using this approach, authors determined in vitro kinetics fibril...
Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on chromosome. It has been proposed to find these fast and accurately, TFs combine one-dimensional (1D) sliding DNA with 3D diffusion in cytoplasm. This facilitated mechanism demonstrated vitro, but it not shown experimentally be exploited living cells. We have developed a single-molecule assay allows us investigate process bacteria. Here we show lac repressor slides 45 ± 10 base...
Fractals are patterns that self-similar across multiple length-scales
In nanotechnology, strategies for the creation and manipulation of nanoparticles in gas phase are critically important surface modification substrate-free characterization. Recent coherent diffractive imaging with intense femtosecond X-ray pulses has verified capability single-shot nanoscale objects at suboptical resolutions beyond radiation-induced damage threshold. By intercepting electrospray-generated particles a single 15 soft-X-ray pulse, we demonstrate specimen free flight first time,...
Many protein condensates can convert to fibrillar aggregates, but the underlying mechanisms are unclear. Liquid–liquid phase separation (LLPS) of spider silk proteins, spidroins, suggests a regulatory switch between both states. Here, we combine microscopy and native mass spectrometry investigate influence sequence, ions, domains on spidroin LLPS. We find that salting out-effects drive LLPS via low-affinity stickers in repeat domains. Interestingly, conditions enable simultaneously cause...
During electrospray ionization (ESI), proteins are transferred from solution into vacuum, a process that influences the conformation of protein. Exactly how much changes due to dehydration process, and in what way, is difficult determine experimentally. The aim this study therefore monitor happens protein structures as surrounding waters gradually evaporate, using computer simulations transition water vacuum. Five different have been simulated with shells varying thickness, enabling us mimic...
Significance Transcription factors (TFs) are the major regulators of gene expression. We have used a combination computer simulations and theoretical methods to explore atomic details for how model TF, lac repressor, moves on DNA in search its specific binding site. find that it slides along helical path, which allows probe groove. The uniqueness study lies fully atomistic molecular dynamics us estimate microscopic interaction energies from TF-DNA structure we developed tool derive...
We have developed a method combining microfluidics, time-lapsed single-molecule microscopy and automated image analysis allowing for the observation of an excess 3000 complete cell cycles exponentially growing Escherichia coli cells per experiment. The makes it possible to analyse rate gene expression at level single proteins over bacterial cycle. also demonstrate that is count number non-specifically DNA binding LacI-Venus molecules using short excitation light pulses. transcription factors...
Abstract Na + /H antiporters are found in all kingdoms of life and exhibit catalysis rates that among the fastest known secondary-active transporters. Here we combine ion mobility mass spectrometry molecular dynamics simulations to study conformational stability lipid-binding properties exchanger NapA from Thermus thermophilus compare this prototypical antiporter NhaA Escherichia coli human homologue NHA2. We find NHA2, but not NhaA, form stable dimers do selectively retain membrane lipids....
Oligomeric proteins assemble with exceptional selectivity, even in the presence of closely related proteins, to perform their cellular roles. We show that most by gene duplication an oligomeric ancestor have evolved avoid hetero-oligomerization and this correlates acquisition distinct functions. report how coassembly is avoided two small heat-shock protein paralogs. A hierarchy assembly, involving intermediates are populated only fleetingly at equilibrium, ensures selective oligomerization....
Liquid–liquid phase separation (LLPS) of heterogeneous ribonucleoproteins (hnRNPs) drives the formation membraneless organelles, but structural information about their assembled states is still lacking. Here, we address this challenge through a combination protein engineering, native ion mobility mass spectrometry, and molecular dynamics simulations. We used an LLPS-compatible spider silk domain pH changes to control self-assembly hnRNPs FUS, TDP-43, hCPEB3, which are implicated in...
Disordered regions are an important functional feature of many multidomain proteins. A prime example is proteins in membraneless organelles, which contain folded domains that engage specific interactions and disordered low-complexity (LC) mediate liquid-liquid phase separation. Studying these complex architectures remains challenging due to their conformational variability. Native mass spectrometry (nMS) routinely employed analyze conformations or proteins; however, its ability with LC has...
Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find spatial...
Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find spatial...
Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find spatial...
Electrospray ionization is a gentle method for sample delivery, routinely used in gas-phase studies of proteins. It crucial structural investigations that the protein structure preserved, and good understanding how affected by transition to gas phase needed tuning experiments meet requirement. Small amounts residual solvent have been shown protect protein, but temperature important too, although it not well understood latter affects details. Using molecular dynamics we simulated four...