How Post-Translational Modifications Influence Amyloid Formation: A Systematic Study of Phosphorylation and Glycosylation in Model Peptides

2010 ◽  
Vol 16 (26) ◽  
pp. 7881-7888 ◽  
Author(s):  
Malgorzata Broncel ◽  
Jessica A. Falenski ◽  
Sara C. Wagner ◽  
Christian P. R. Hackenberger ◽  
Beate Koksch
Keyword(s):  
Systematic Study ◽  
Amyloid Formation ◽  
Post Translational Modifications ◽  
Model Peptides

The role of metal ions in amyloid formation: general principles from model peptides

Metallomics ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. 183 ◽  
Author(s):  
Bruno Alies ◽  
Christelle Hureau ◽  
Peter Faller
Keyword(s):  
Metal Ions ◽  
Amyloid Formation ◽  
Model Peptides

Histone mimics: more tales to read

2021 ◽  
Vol 478 (14) ◽  
pp. 2789-2791
Author(s):  
Yucong Yu ◽  
Hong Wen ◽  
Xiaobing Shi
Keyword(s):  
Systematic Study ◽  
Histone H3 ◽  
Chromatin Accessibility ◽  
Chromatin Regulation ◽  
Histone Proteins ◽  
Post Translational Modifications ◽  
Epigenetic Marks ◽  
The Status

Post-translational modifications (PTMs) on histone proteins are known as epigenetic marks that demarcate the status of chromatin. These modifications are ‘read' by specific reader proteins, which in turn recruit additional factors to modulate chromatin accessibility and the activity of the underlying DNA. Accumulating evidence suggests that these modifications are not restricted solely to histones, many non-histone proteins may function in a similar way through mimicking the histones. In this commentary, we briefly discuss a systematic study of the discovery of histone H3 N-terminal mimicry proteins (H3TMs), and their implications in chromatin regulation and drug discoveries.

A Systematic Study of the Effect of Physiological Factors on β2-Microglobulin Amyloid Formation at Neutral pH†

Biochemistry ◽  
2006 ◽  
Vol 45 (7) ◽  
pp. 2311-2321 ◽  
Author(s):  
Sarah L. Myers ◽  
Susan Jones ◽  
Thomas R. Jahn ◽  
Isobel J. Morten ◽  
Glenys A. Tennent ◽  
...  
Keyword(s):  
Systematic Study ◽  
Amyloid Formation ◽  
Physiological Factors ◽  
Β2 Microglobulin ◽  
Neutral Ph

scholarly journals Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lynn Radamaker ◽  
Sara Karimi-Farsijani ◽  
Giada Andreotti ◽  
Julian Baur ◽  
Matthias Neumann ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Germ Line ◽  
Somatic Hypermutation ◽  
Ex Vivo ◽  
The Body ◽  
Al Amyloidosis ◽  
Amyloid Formation ◽  
Post Translational Modifications ◽  
Fibril Morphology ◽  
Al Amyloid

AbstractSystemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here we present the cryo electron microscopy (cryo-EM) structure of an ex vivo λ1-AL amyloid fibril whose deposits disrupt the ordered cardiomyocyte structure in the heart. The fibril protein contains six mutational changes compared to the germ line and three PTMs (disulfide bond, N-glycosylation and pyroglutamylation). Our data imply that the disulfide bond, glycosylation and mutational changes contribute to determining the fibril protein fold and help to generate a fibril morphology that is able to withstand proteolytic degradation inside the body.

Zinc(II) modulates specifically amyloid formation and structure in model peptides

2010 ◽  
Vol 16 (2) ◽  
pp. 333-340 ◽  
Author(s):  
Bruno Alies ◽  
Vincent Pradines ◽  
Isabelle Llorens-Alliot ◽  
Stéphanie Sayen ◽  
Emmanuel Guillon ◽  
...  
Keyword(s):  
Amyloid Formation ◽  
Model Peptides

Quantitative parallel EELS spectrum imaging developed as a new tool in AEM

1992 ◽  
Vol 50 (2) ◽  
pp. 1202-1203
Author(s):  
Gianluigi Botton ◽  
Gilles L'espérance
Keyword(s):  
Statistical Analysis ◽  
Spatial Resolution ◽  
Personal Computer ◽  
Systematic Study ◽  
Present Author ◽  
Chemical Elements ◽  
Detection Limits ◽  
Research Groups ◽  
Quantitative Performance ◽  
Spectrum Imaging

As interest for parallel EELS spectrum imaging grows in laboratories equipped with commercial spectrometers, different approaches were used in recent years by a few research groups in the development of the technique of spectrum imaging as reported in the literature. Either by controlling, with a personal computer both the microsope and the spectrometer or using more powerful workstations interfaced to conventional multichannel analysers with commercially available programs to control the microscope and the spectrometer, spectrum images can now be obtained. Work on the limits of the technique, in terms of the quantitative performance was reported, however, by the present author where a systematic study of artifacts detection limits, statistical errors as a function of desired spatial resolution and range of chemical elements to be studied in a map was carried out The aim of the present paper is to show an application of quantitative parallel EELS spectrum imaging where statistical analysis is performed at each pixel and interpretation is carried out using criteria established from the statistical analysis and variations in composition are analyzed with the help of information retreived from t/γ maps so that artifacts are avoided.

Reading the phosphorylation code: binding of the 14-3-3 protein to multivalent client phosphoproteins

2020 ◽  
Vol 477 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Nikolai N. Sluchanko
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Protein ◽  
Structural Basis ◽  
Major Protein ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Biochemical Journal ◽  
Multiple Binding ◽  
And Control

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

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