A5058049092- Prion Diseases and Protein Misfolding
- Heat shock proteins research
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Trace Elements in Health
- Neurological diseases and metabolism
- Enzyme Structure and Function
- RNA Research and Splicing
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Supramolecular Self-Assembly in Materials
- Biotin and Related Studies
- Toxin Mechanisms and Immunotoxins
- Advanced biosensing and bioanalysis techniques
- Viral gastroenteritis research and epidemiology
- Chromatin Remodeling and Cancer
- Cancer Mechanisms and Therapy
- thermodynamics and calorimetric analyses
- Protein Degradation and Inhibitors
- Redox biology and oxidative stress
- Cancer-related Molecular Pathways
- 14-3-3 protein interactions
- Nuclear Receptors and Signaling
Institute of Biophysics
2014-2023
Chinese Academy of Sciences
2014-2023
University of Chinese Academy of Sciences
2017-2023
Beijing Chaoyang Emergency Medical Center
2020
Center for Excellence in Education
2017-2020
University of Cambridge
1996-2014
Public Health Wales
2014
Czech Academy of Sciences, Institute of Biophysics
2011
Choose your poison: Chiral CdTe quantum dots (QDs) coated with L- or D-glutathione (GSH) stabilizers exhibit differences in cytotoxicity although they have identical composition and size. D-GSH-QDs are less cytotoxic than L-GSH-QDs. The ability of QDs to induce cell death is correlated their autophagy, which chirality-dependent (see picture). Detailed facts importance specialist readers published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited typeset. They...
Significance Protein oligomers are a fundamental component of amyloidogenic disorders such as Alzheimer’s disease, being both critical intermediates in the formation amyloid fibrils and most toxic species on protein aggregation pathway. Here, we derive general analytical expressions for chemical kinetics generated during amyloid-formation reactions explain how these may be used to categorize according their basic physicochemical properties. By applying this framework experimental kinetic...
Liquid–liquid phase separation (LLPS) of proteins into biomolecular condensates has emerged as a fundamental principle underpinning cellular function and malfunction. Indeed, many human pathologies, including protein misfolding diseases, are linked to aberrant liquid-to-solid transitions, disease-associated aggregates often nucleate through separation. The molecular level determinants that promote pathological transitions remain, however, poorly understood. Here we study LLPS the...
SummaryIn budding yeast, the essential functions of Hsp70 chaperones Ssa1–4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation Ssa1 T36 within cyclin-dependent kinase (CDK) consensus site conserved among proteins alters client interactions. triggers displacement Ydj1, allowing to bind G1 cyclin Cln3 promote its degradation. The stress CDK Pho85 phosphorylates upon nitrogen starvation or...
The chaperonin GroEL is a large complex composed of 14 identical 57-kDa subunits that requires ATP and GroES for some its activities. We find monomeric polypeptide corresponding to residues 191 345 has the activity tetradecamer both in facilitating refolding rhodanese cyclophilin A absence catalyzing unfolding native barnase. Its crystal structure, solved at 2.5 resolution, shows well-ordered domain with same fold as intact GroEL. have thus isolated active site allosteric molecular...
Hydrogen-deuterium exchange of 39 amide protons Bacillus amyloliquefaciens ribonuclease (barnase) was analyzed by two-dimensional nuclear magnetic resonance in the presence micromolar concentrations molecular chaperones GroEL and SecB. Both bound to native barnase under physiological conditions catalyzed deeply buried with solvent. Such required complete unfolding barnase, which occurred complex chaperones. Subsequent collapse unfolded exchange-protected folding intermediate markedly slowed...
Abstract This manuscript describes a new and general method to identify proteins localized into spatially restricted membrane microenvironments. Horseradish peroxidase (HRP) is brought contact with target protein by being covalently linked primary or secondary antibody, an antigen substrate, drug, toxin. A biotinylated tyramide‐based reagent then added. In the presence of HRP hydrogen peroxide, converted free radical that only diffuses short distance before labeling within few tens hundreds...
Preventing tau aggregation is a potential therapeutic strategy in Alzheimer's disease and other tauopathies. Recently, liquid-liquid phase separation has been found to facilitate the formation of pathogenic conformations fibrillar aggregates, although many aspects conformational transitions during transition process remain unknown. Here, we demonstrate that inhibitor methylene blue promotes accelerates liquid-to-gel droplets independent redox activity blue. We further show inhibits...
Ure2p is the precursor protein of Saccharomyces cerevisiae prion [URE3]. shows homology to glutathione transferases but lacks typical transferase activity. A recent study found that deletion Ure2 gene causes increased sensitivity heavy metal ions and oxidants, whereas strains show normal sensitivity. To demonstrate protection against oxidant toxicity an inherent property native requires biochemical characterization purified protein. Here we use steady-state kinetic methods characterize...
Abstract Background The microtubule associated protein tau is the principle component of neurofibrillar tangles, which are a characteristic marker in pathology Alzheimer's disease; similar lesions also observed after chronic alcohol abuse. Formaldehyde common environmental contaminant and metabolite methanol. Although many studies have been done on methanol formaldehyde intoxication, none these address contribution misfolding to pathological mechanism, particular effect conformation...
The self-assembly of polypeptides into amyloid structures is associated with a range increasingly prevalent neurodegenerative diseases as well select set functional processes in biology. phenomenon results species dramatically different sizes, from small oligomers to large fibrils; however, the kinetic relationship between these challenging characterize. In case prion aggregates, can self-replicate and act infectious agents. Here we use single molecule spectroscopy obtain quantitative...
Efficient multiple-electron redox reactions are performed by galactoase oxidase, cysteine dioxygenase, sulfite reductase, and cytochrome c nitrite reductase. A post-translationally modified tyrosine–cysteine cross-link (Tyr-Cys) in their active sites is essential for functions. Detailed facts of importance to specialist readers published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted the authors. Please note: The...
Amyloid fibrils represent a generic class of protein structure associated with both pathological states and naturally occurring functional materials. This nanostructure has recently also emerged as an excellent foundation for sophisticated biocompatible materials including scaffolds carriers biologically active molecules. Protein-based offer the potential advantage that additional functions can be directly incorporated via gene fusion producing single chimeric polypeptide will self-assemble...
DnaK is the major bacterial Hsp70, participating in DNA replication, protein folding, and stress response. cooperates with Hsp40 co-chaperone DnaJ nucleotide exchange factor GrpE. Under non-stress conditions, binds to heat shock transcription σ(32)and facilitates its degradation. Oxidative results temporary inactivation of due depletion cellular ATP thiol modifications such as glutathionylation until normal levels a reducing environment are restored. However, biological significance remains...
Hsp70 is a conserved molecular chaperone that plays an indispensable role in regulating protein folding, translocation, and degradation. The conformational dynamics of its regulation by cochaperones are vital to function. Using bulk single-molecule fluorescence resonance energy transfer (smFRET) techniques, we studied the interdomain distribution human stress-inducible Hsp70A1 kinetics changes induced nucleotide Hsp40 cochaperone Hdj1. We found conformations between within nucleotide-...
The conversion of intrinsically disordered Tau to highly ordered amyloid aggregates is associated with a wide range neurodegenerative diseases termed tauopathies. presence lipid bilayer membranes critical factor that accelerates the abnormal aggregation protein. However, membrane-induced conformational changes and mechanism for accelerated fibrillation remain elusive. In this study, single-molecule Förster resonance energy transfer (smFRET) fluorescence correlation spectroscopy (FCS) were...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRelationship between Equilibrium Amide Proton Exchange Behavior and the Folding Pathway of BarnaseSarah Perrett, Jane Clarke, Andrea M. Hounslow, Alan R. FershtCite this: Biochemistry 1995, 34, 29, 9288–9298Publication Date (Print):July 25, 1995Publication History Published online1 May 2002Published inissue 25 July 1995https://pubs.acs.org/doi/10.1021/bi00029a003https://doi.org/10.1021/bi00029a003research-articleACS PublicationsRequest reuse...