Prediction of Protein Aggregation and Amyloid Formation

2017 ◽  
pp. 205-263 ◽  
Author(s):  
Ricardo Graña-Montes ◽  
Jordi Pujols-Pujol ◽  
Carlota Gómez-Picanyol ◽  
Salvador Ventura
Keyword(s):  
Protein Aggregation ◽  
Amyloid Formation

scholarly journals Valorization of Apple Peels through the Study of the Effects on the Amyloid Aggregation Process of κ-Casein

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2371
Author(s):  
Valeria Guarrasi ◽  
Giacoma Cinzia Rappa ◽  
Maria Assunta Costa ◽  
Fabio Librizzi ◽  
Marco Raimondo ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Environmental Sustainability ◽  
Bovine Milk ◽  
Amyloid Formation ◽  
Aggregation Process ◽  
Amyloid Aggregation ◽  
Social Challenges ◽  
Force Microscopy ◽  
Atomic Force ◽  
Apple Peels

Waste valorization represents one of the main social challenges when promoting a circular economy and environmental sustainability. Here, we evaluated the effect of the polyphenols extracted from apple peels, normally disposed of as waste, on the amyloid aggregation process of κ-casein from bovine milk, a well-used amyloidogenic model system. The effect of the apple peel extract on protein aggregation was examined using a thioflavin T fluorescence assay, Congo red binding assay, circular dichroism, light scattering, and atomic force microscopy. We found that the phenolic extract from the peel of apples of the cultivar “Fuji”, cultivated in Sicily (Caltavuturo, Italy), inhibited κ-casein fibril formation in a dose-dependent way. In particular, we found that the extract significantly reduced the protein aggregation rate and inhibited the secondary structure reorganization that accompanies κ-casein amyloid formation. Protein-aggregated species resulting from the incubation of κ-casein in the presence of polyphenols under amyloid aggregation conditions were reduced in number and different in morphology.

scholarly journals Suppression of aggregate and amyloid formation by a novel intrinsically disordered region in metazoan Hsp110 chaperones

2021 ◽  
Author(s):  
Unekwu M. Yakubu ◽  
Kevin A. Morano
Keyword(s):  
Protein Aggregation ◽  
Molecular Chaperones ◽  
Citrate Synthase ◽  
Neuronal Cell ◽  
Amyloid Formation ◽  
Nucleotide Exchange ◽  
Aggregation Assay ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region

AbstractMolecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is related to the canonical Hsp70 class of protein folding molecular chaperones and interacts with Hsp70 as a nucleotide exchange factor (NEF), promoting rapid cycling of ADP for ATP. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles remain undefined. Previous work in Drosophila melanogaster has shown that loss of the sole Hsp110 gene (Hsc70cb) accelerates the aggregation of polyglutamine (polyQ)-expanded human Huntingtin, while its overexpression protects against polyQ-mediated neuronal cell death. We hypothesize that in addition to its role as an Hsp70 NEF, Drosophila Hsp110 may function in the fly as a protective protein “holdase”, preventing the aggregation of unfolded polypeptides via the SBD-β subdomain. Using an in vitro protein aggregation assay we demonstrate for the first time that Drosophila Hsp110 effectively prevents aggregation of the model substrate citrate synthase. We also report the discovery of a redundant and heretofore unknown potent holdase capacity in a 138 amino-acid region of Hsp110 carboxyl-terminal to both SBD-β and SBD-α (henceforth called the C-terminal extension). This sequence is highly conserved in metazoan Hsp110 genes, completely absent from fungal representatives, including Saccharomyces cerevisiae SSE1, and is computationally predicted to contain an intrinsically disordered region (IDR). We demonstrate that this IDR sequence within the human Hsp110s, Apg-1 and Hsp105α, inhibits the formation of amyloid Aβ-42 and α-synuclein fibrils in vitro but cannot mediate fibril disassembly. Together these findings demonstrate the existence of a second independent, passive holdase property of metazoan Hsp110 chaperones capable of suppressing both general protein aggregation and amyloidogenesis and raise the possibility of exploitation of this IDR for therapeutic benefit in combating neurodegenerative disease.

scholarly journals The Materials Science of Protein Aggregation

MRS Bulletin ◽  
2005 ◽  
Vol 30 (6) ◽  
pp. 452-457 ◽  
Author(s):  
D.L. Cox ◽  
H. Lashuel ◽  
K.Y.C. Lee ◽  
R.R.P. Singh
Keyword(s):  
Protein Aggregation ◽  
Conformational Change ◽  
Lipid Bilayers ◽  
Materials Science ◽  
Prion Diseases ◽  
Protein Structures ◽  
Biochemical Networks ◽  
Amyloid Formation ◽  
Biological Phenomena

AbstractNumerous human diseases are associated with conformational change and aggregation of proteins, including Alzheimer's, Parkinson's, prion diseases (such as mad cow disease), familial amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), Huntington's, and type II (mature onset) diabetes. In many cases, it has been demonstrated that conformational change and aggregation can occur outside living cells and complex biochemical networks. Hence, approaches from materials and physical science have enhanced our understanding of the role of protein aggregation in these diseases at the molecular and nanoscale levels. In this article, we will review what is known about these protein structures from the perspective of materials science, focusing on the details of emergent oligomeric and nanotube-like structures, their interactions with model lipid bilayers, how the structures relate to observed biological phenomena, and how protein aggregation and amyloid formation can be employed for the good in biology and materials science.

scholarly journals Making Milk Less Allergenic

2018 ◽  
Vol 4 (1) ◽  
pp. 27-32
Author(s):  
Fiona A. Ewart
Keyword(s):  
Protein Aggregation ◽  
Gel Electrophoresis ◽  
Milk Protein ◽  
Grocery Store ◽  
Amyloid Formation ◽  
Allergenic Food ◽  
Milk Allergy ◽  
Cranberry Juice ◽  
Milk Products ◽  
Ige Binding

The formation of stable aggregates by food proteins is associated with allergenicity. In particular, amyloid formation by the fish allergen parvalbumin was recently shown to favor IgE binding and subsequent allergic recognition. Therefore, reducing amyloid content in an allergenic food might offer a direct way to make that food less likely to trigger an allergy. In this project, protein aggregation and amyloid formation were studied in milk using gel electrophoresis and fluorescence-based assays. The results suggested that ordinary pasteurized milk from the grocery store contained protein aggregates and specifically amyloid. Processing the milk as normally done during food preparation did not appreciably affect general aggregation or amyloid formation. However, the addition of some polyphenol-containing food products to the milk appeared to result in reduced amyloid levels. Moreover, cranberry juice also appeared to reduce amyloid formation by the milk protein casein. These results suggest that the addition of cranberry or other polyphenol-rich foods to milk products for young children may reduce the risk of milk allergy development by diminishing protein aggregation.

scholarly journals The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation

2020 ◽  
Author(s):  
Anita Pras ◽  
Bert Houben ◽  
Francesco A. Aprile ◽  
Renée Seinstra ◽  
Rodrigo Gallardo ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Structural Changes ◽  
Colloidal Stability ◽  
Positive Charge ◽  
Amyloid Formation ◽  
Related Protein ◽  
Age Related ◽  
Related Proteins ◽  
Protein Toxicity ◽  
Charge Interactions

AbstractWhile aggregation-prone proteins are known to accelerate ageing and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A and SERF2 have recently been identified as cellular modifiers of such cytotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with specific patterns of negatively charged and hydrophobic, aromatic amino acids. The absence of such patterns, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In a protein aggregation model in the nematode C. elegans, protein aggregation was suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that charge interactions are required for MOAG-4 and SERF2 to promote aggregation. Such charged interactions might accelerate the primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our finding that negatively charged segments are overrepresented in amyloid-forming proteins suggests that inhibition of charge interactions deserves exploration as a strategy to target age-related protein toxicity.Significance StatementHow aging causes relatively common diseases such as Alzheimer’s and Parkinson’s is still a mystery. Since toxic structural changes in proteins are likely to be responsible, we investigated biological mechanisms that could drive such changes. We made use of a modifying factor called SERF2, which accelerates structural changes and aggregation of several disease-related proteins. Through a peptide-binding screen, we found that SERF2 acts on negatively charged protein regions. The abundance of such regions in the disease-related proteins explains why SERF has its effect. Removing positive charge in SERF was sufficient to suppress protein aggregation in models for disease. We propose that blocking charge-interactions with SERF or other modifiers could serve as a general approach to treat age-related protein toxicity.

scholarly journals Ribosylation induced structural changes in Bovine Serum Albumin: understanding high dietary sugar induced protein aggregation and amyloid formation

Heliyon ◽  
2020 ◽  
Vol 6 (9) ◽  
pp. e05053
Author(s):  
Ahana Das ◽  
Pijush Basak ◽  
Arnab Pramanik ◽  
Rajib Majumder ◽  
Avishek Ghosh ◽  
...  
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Protein Aggregation ◽  
Bovine Serum ◽  
Structural Changes ◽  
Amyloid Formation ◽  
Dietary Sugar
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