Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Abundant fish protein inhibits ?-synuclein amyloid formation.

ABSTRACT: The most common allergen in fish, the highly-abundant protein ?-parvalbumin, forms amyloid structures as a way to avoid gastrointestinal degradation and transit to the blood. In humans, the same amyloid structures are mostly associated with neurodegenerative disorders such as Alzheimer's and Parkinson's. We here assessed a putative connection between these amyloids using recombinant Atlantic cod ?-parvalbumin and the key amyloidogenic protein in Parkinson's disease, ?-synuclein. Using a set of in vitro biophysical methods, we discovered that ?-parvalbumin readily inhibits amyloid formation of ?-synuclein. The underlying mechanism was found to involve ?-synuclein binding to the surface of ?-parvalbumin amyloid fibers. In addition to being a new amyloid inhibition mechanism, the data suggest that health benefits of fish may be explained in part by cross-reaction of ?-parvalbumin with human amyloidogenic proteins.

SUBMITTER: Werner T

PROVIDER: S-EPMC5882657 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Abundant fish protein inhibits α-synuclein amyloid formation.

Werner Tony T Kumar Ranjeet R Horvath Istvan I Scheers Nathalie N Wittung-Stafshede Pernilla P

Scientific reports 20180403 1

The most common allergen in fish, the highly-abundant protein β-parvalbumin, forms amyloid structures as a way to avoid gastrointestinal degradation and transit to the blood. In humans, the same amyloid structures are mostly associated with neurodegenerative disorders such as Alzheimer's and Parkinson's. We here assessed a putative connection between these amyloids using recombinant Atlantic cod β-parvalbumin and the key amyloidogenic protein in Parkinson's disease, α-synuclein. Using a set of i ...[more]

PMID: 29615738

Similar Datasets

Ganglioside lipids accelerate ?-synuclein amyloid formation.

Project description:The deposition of ?-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of ?-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of ?-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational change and only weakly catalyse aggregation. Intriguingly, aggregation was also triggered by free ganglioside headgroups, while these caused no conformational change of ?-synuclein monomers. Our data reveal that partially folded ?-synuclein helical intermediates are not required species in triggering of ?-synuclein aggregation.

| S-EPMC6121081 | biostudies-other

Freezing of a fish antifreeze protein results in amyloid fibril formation.

Project description:Amyloid is associated with a number of diseases including Alzheimer's, Huntington's, Parkinson's, and the spongiform encephalopathies. Amyloid fibrils have been formed in vitro from both disease and nondisease related proteins, but the latter requires extremes of pH, heat, or the presence of a chaotropic agent. We show, using fluorescence spectroscopy, electron microscopy, and solid-state NMR spectroscopy, that the alpha-helical type I antifreeze protein from the winter flounder forms amyloid fibrils at pH 4 and 7 upon freezing and thawing. Our results demonstrate that the freezing of some proteins may accelerate the formation of amyloid fibrils.

| S-EPMC1302635 | biostudies-literature

Interactions between SARS-CoV-2 N-Protein and α-Synuclein Accelerate Amyloid Formation.

Project description:First cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson's disease (PD) have been reported. Currently, it is unclear if there is also a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of α-synuclein protein into amyloid fibrils characteristic for PD, we investigated the effect of the presence of SARS-CoV-2 proteins on α-synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 spike protein (S-protein) has no effect on α-synuclein aggregation, while SARS-CoV-2 nucleocapsid protein (N-protein) considerably speeds up the aggregation process. We observe the formation of multiprotein complexes and eventually amyloid fibrils. Microinjection of N-protein in SH-SY5Y cells disturbed the α-synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as molecular basis for the observed correlation between SARS-CoV-2 infections and Parkinsonism.

| S-EPMC8739828 | biostudies-literature

An engineered monomer binding-protein for ?-synuclein efficiently inhibits the proliferation of amyloid fibrils.

Project description:Removing or preventing the formation of [Formula: see text]-synuclein aggregates is a plausible strategy against Parkinson's disease. To this end, we have engineered the [Formula: see text]-wrapin AS69 to bind monomeric [Formula: see text]-synuclein with high affinity. In cultured cells, AS69 reduced the self-interaction of [Formula: see text]-synuclein and formation of visible [Formula: see text]-synuclein aggregates. In flies, AS69 reduced [Formula: see text]-synuclein aggregates and the locomotor deficit resulting from [Formula: see text]-synuclein expression in neuronal cells. In biophysical experiments in vitro, AS69 highly sub-stoichiometrically inhibited both primary and autocatalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69-[Formula: see text]-synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition of secondary nucleation. These results represent a new paradigm that high affinity monomer binders can lead to strongly sub-stoichiometric inhibition of nucleation processes.

| S-EPMC6721797 | biostudies-literature

Charge Regulation during Amyloid Formation of α-Synuclein.

Project description:Electrostatic interactions play crucial roles in protein function. Measuring pKa value perturbations upon complex formation or self-assembly of e.g. amyloid fibrils gives valuable information about the effect of electrostatic interactions in those processes. Site-specific pKa value determination by solution NMR spectroscopy is challenged by the high molecular weight of amyloid fibrils. Here we report a pH increase during fibril formation of α-synuclein, observed using three complementary experimental methods: pH electrode measurements in water; colorimetric changes of a fluorescent indicator; and chemical shift changes for histidine residues using solution state NMR spectroscopy. A significant pH increase was detected during fibril formation in water, on average by 0.9 pH units from 5.6 to 6.5, showing that protons are taken up during fibril formation. The pH upshift was used to calculate the average change in the apparent pKaave value of the acidic residues, which was found to increase by at least 1.1 unit due to fibril formation. Metropolis Monte Carlo simulations were performed on a comparable system that also showed a proton uptake due to fibril formation. Fibril formation moreover leads to a significant change in proton binding capacitance. Parallel studies of a mutant with five charge deletions in the C-terminal tail revealed a smaller pH increase due to fibril formation, and a smaller change (0.5 units on average) in the apparent pKaave values of the acidic residues. We conclude that the proton uptake during the fibril formation is connected to the high density of acidic residues in the C-terminal tail of α-synuclein.

| S-EPMC8161422 | biostudies-literature

Hydrogen sulfide inhibits amyloid formation.

Project description:Amyloid fibrils are large aggregates of misfolded proteins, which are often associated with various neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and vascular dementia. The amount of hydrogen sulfide (H2S) is known to be significantly reduced in the brain tissue of people diagnosed with Alzheimer's disease relative to that of healthy individuals. These findings prompted us to investigate the effects of H2S on the formation of amyloids in vitro using a model fibrillogenic protein hen egg white lysozyme (HEWL). HEWL forms typical ?-sheet rich fibrils during the course of 70 min at low pH and high temperatures. The addition of H2S completely inhibits the formation of ?-sheet and amyloid fibrils, as revealed by deep UV resonance Raman (DUVRR) spectroscopy and ThT fluorescence. Nonresonance Raman spectroscopy shows that disulfide bonds undergo significant rearrangements in the presence of H2S. Raman bands corresponding to disulfide (RSSR) vibrational modes in the 550-500 cm(-1) spectral range decrease in intensity and are accompanied by the appearance of a new 490 cm(-1) band assigned to the trisulfide group (RSSSR) based on the comparison with model compounds. The formation of RSSSR was proven further using a reaction with TCEP reduction agent and LC-MS analysis of the products. Intrinsic tryptophan fluorescence study shows a strong denaturation of HEWL containing trisulfide bonds. The presented evidence indicates that H2S causes the formation of trisulfide bridges, which destabilizes HEWL structure, preventing protein fibrillation. As a result, small spherical aggregates of unordered protein form, which exhibit no cytotoxicity by contrast with HEWL fibrils.

| S-EPMC4315425 | biostudies-literature

α-Synuclein-derived lipoparticles in the study of α-Synuclein amyloid fibril formation.

Project description:Aggregation of the protein α-Synuclein (αSyn) is of great interest due to its involvement in the pathology of Parkinson's disease. However, under in vitro conditions αSyn is very soluble and kinetically stable for extended time periods. As a result, most αSyn aggregation assays rely on conditions that artificially induce or enhance aggregation, often by introducing rather non-native conditions. It has been shown that αSyn interacts with membranes and conditions have been identified in which membranes can promote as well as inhibit αSyn aggregation. It has also been shown that αSyn has the intrinsic capability to assemble lipid-protein-particles, in a similar way as apolipoproteins can form lipid-bilayer nanodiscs. Here we show that these αSyn-lipid particles (αSyn-LiPs) can also effectively induce, accelerate or inhibit αSyn aggregation, depending on the applied conditions. αSyn-LiPs therefore provide a general platform and additional tool, complementary to other setups, to study various aspects of αSyn amyloid fibril formation.

| S-EPMC6451039 | biostudies-literature

Membrane remodeling by ?-synuclein and effects on amyloid formation.

Project description:?-Synuclein (?-Syn), an intrinsically disordered protein, is associated with Parkinson's disease. Though molecular pathogenic mechanisms are ill-defined, mounting evidence connects its amyloid forming and membrane binding propensities to disease etiology. Contrary to recent data suggesting that membrane remodeling by ?-syn involves anionic phospholipids and helical structure, we discovered that the protein deforms vesicles with no net surface charge (phosphatidylcholine, PC) into tubules (average diameter ?20 nm). No discernible secondary structural changes were detected by circular dichroism spectroscopy upon the addition of vesicles. Notably, membrane remodeling inhibits ?-syn amyloid formation affecting both lag and growth phases. Using five single tryptophan variants and time-resolved fluorescence anisotropy measurements, we determined that ?-syn influences bilayer structure with surprisingly weak interaction and no site specificity (partition constant, Kp ? 300 M(-1)). Vesicle deformation by ?-syn under a variety of different lipid/protein conditions is characterized via transmission electron microscopy. As cellular membranes are enriched in PC lipids, these results support possible biological consequences for ?-syn induced membrane remodeling related to both function and pathogenesis.

| S-EPMC3859146 | biostudies-literature

Stimulation of ?-synuclein amyloid formation by phosphatidylglycerol micellar tubules.

Project description:?-Synuclein (?-Syn) is a presynaptic protein that is accumulated in its amyloid form in the brains of Parkinson's patients. Although its biological function remains unclear, ?-syn has been suggested to bind to synaptic vesicles and facilitate neurotransmitter release. Recently, studies have found that ?-syn induces membrane tubulation, highlighting a potential mechanism for ?-syn to stabilize highly curved membrane structures which could have both functional and dysfunctional consequences. To understand how membrane remodeling by ?-syn affects amyloid formation, we have studied the ?-syn aggregation process in the presence of phosphatidylglycerol (PG) micellar tubules, which were the first reported example of membrane tubulation by ?-syn. Aggregation kinetics, ?-sheet content, and macroscopic protein-lipid structures were observed by Thioflavin T fluorescence, circular dichroism spectroscopy and transmission electron microscopy, respectively. Collectively, the presence of PG micellar tubules formed at a stochiometric (L/P?=?1) ratio was found to stimulate ?-syn fibril formation. Moreover, transmission electron microscopy and solid-state nuclear magnetic resonance spectroscopy revealed the co-assembly of PG and ?-syn into fibril structures. However, isolated micellar tubules do not form fibrils by themselves, suggesting an important role of free ?-syn monomers during amyloid formation. In contrast, fibrils did not form in the presence of excess PG lipids (?L/P?=?50), where most of the ?-syn molecules are in a membrane-bound ?-helical form. Our results provide new mechanistic insights into how membrane tubules modulate ?-syn amyloid formation and support a pivotal role of protein-lipid interaction in the dysfunction of ?-syn.

| S-EPMC6125227 | biostudies-literature

Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein.

Project description:The protein alpha-synuclein (?S) self-assembles into toxic beta-sheet aggregates in Parkinson's disease, while it is proposed that ?S forms soluble alpha-helical multimers in healthy neurons. Here, we have made ?S multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule F?rster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of ?S form less multimers than wild-type ?S. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of ?S in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during ?S fibrillation.

| S-EPMC5037366 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data