107 Result(s)
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Michele Vendruscolo
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Article
Open AccessA metastable subproteome underlies inclusion formation in muscle proteinopathies
Protein aggregation is a pathological feature of neurodegenerative disorders. We previously demonstrated that protein inclusions in the brain are composed of supersaturated proteins, which are abundant and agg...
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Article
Open AccessProbing the dynamic stalk region of the ribosome using solution NMR
We describe an NMR approach based on the measurement of residual dipolar couplings (RDCs) to probe the structural and motional properties of the dynamic regions of the ribosome. Alignment of intact 70S ribosom...
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Article
Open AccessSoluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer’s disease progression
Soluble aggregates of amyloid-β (Aβ) have been associated with neuronal and synaptic loss in Alzheimer’s disease (AD). However, despite significant recent progress, the mechanisms by which these aggregated spe...
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Open AccessIdentifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming
Identifying the A- and P-site locations on ribosome-protected mRNA fragments from Ribo-Seq experiments is a fundamental step in the quantitative analysis of transcriptome-wide translation properties at the cod...
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Article
Open AccessThe free energy landscape of the oncogene protein E7 of human papillomavirus type 16 reveals a complex interplay between ordered and disordered regions
When present, structural disorder makes it very challenging to characterise the conformational properties of proteins. This is particularly the case of proteins, such as the oncogene protein E7 of human papill...
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Article
Open AccessDifferent soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
Protein aggregation is a complex process resulting in the formation of heterogeneous mixtures of aggregate populations that are closely linked to neurodegenerative conditions, such as Alzheimer’s disease. Here...
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Open AccessA method of predicting the in vitro fibril formation propensity of Aβ40 mutants based on their inclusion body levels in E. coli
Overexpression of recombinant proteins in bacteria may lead to their aggregation and deposition in inclusion bodies. Since the conformational properties of proteins in inclusion bodies exhibit many of the char...
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Article
Open AccessTrodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ42) are key pathogenic agents in Alzheimer’s disease (AD). To investigate the relationship bet...
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A Practical Guide to the Simultaneous Determination of Protein Structure and Dynamics Using Metainference
Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of...
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Chapter
Dynamics and Control of Peptide Self-Assembly and Aggregation
The aggregation of proteins into fibrillar structures is a central process implicated in the onset and development of several devastating neuro-degenerative diseases, but can, in contrast to these pathological...
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Article
A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology
Excitatory neurons are preferentially impaired in early Alzheimer’s disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulati...
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Open AccessMicrofluidic deposition for resolving single-molecule protein architecture and heterogeneity
Scanning probe microscopy provides a unique window into the morphology, mechanics, and structure of proteins and their complexes on the nanoscale. Such measurements require, however, deposition of samples onto...
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Open AccessAuthor Correction: The molecular chaperones DNAJB6 and Hsp70 cooperate to suppress α-synuclein aggregation
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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Article
Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes
Alzheimer’s disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer’s diseas...
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Article
Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide
Map** free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach,...
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Article
Open AccessDelivery of Native Proteins into C. elegans Using a Transduction Protocol Based on Lipid Vesicles
The nematode worm Caenorhabditis elegans (C. elegans) is a versatile and widely used animal model for in vivo studies of a broad range of human diseases, in particular for understanding their genetic origins and ...
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Article
Open AccessMethods of probing the interactions between small molecules and disordered proteins
It is generally recognized that a large fraction of the human proteome is made up of proteins that remain disordered in their native states. Despite the fact that such proteins play key biological roles and ar...
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Open AccessThe molecular chaperones DNAJB6 and Hsp70 cooperate to suppress α-synuclein aggregation
A major hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) in certain neuronal tissues. LBs are protein-rich inclusions, in which α-synuclein (α-syn) is the most abundant protein. Since ...
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Article
Open AccessRapid and accurate in silico solubility screening of a monoclonal antibody library
Antibodies represent essential tools in research and diagnostics and are rapidly growing in importance as therapeutics. Commonly used methods to obtain novel antibodies typically yield several candidates capab...
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Article
Open AccessNanobodies raised against monomeric ɑ-synuclein inhibit fibril formation and destabilize toxic oligomeric species
The aggregation of the protein ɑ-synuclein (ɑS) underlies a range of increasingly common neurodegenerative disorders including Parkinson’s disease. One widely explored therapeutic strategy for these conditions...
