scholarly journals Thermostability of lysozyme amyloid fibrils

2021 ◽  
Vol 2086 (1) ◽  
pp. 012117
Author(s):  
N M Melnikova ◽  
M I Sulatsky ◽  
Yu D Diordienko ◽  
A I Sulatskaya
Keyword(s):  
Secondary Structure ◽  
Amyloid Fibrils ◽  
External Factor ◽  
Prion Diseases ◽  
High Strength ◽  
Protein Aggregates ◽  
Structure And Stability ◽  
External Influences ◽  
Intramolecular Mobility ◽  
The Stability

Abstract Ordered protein aggregates, amyloid fibrils, are a marker of many serious diseases, such as Alzheimer’s, Parkinson’s, prion diseases, etc. At present, special attention is paid to the study of external influences that can affect the structure and stability of mature amyloid fibrils, which may be in demand in the development of approaches to the therapy of amyloidosis, as well as in the creation of new high-strength materials on the basis of these protein aggregates. An external factor, the influence of which on fibrils was studied in this work, was temperature denaturation. It was shown that heating lysozyme amyloid fibrils to 60 °C does not lead to their degradation, but leads only to a reversible increase in the intramolecular mobility of amyloid-forming proteins, but does not change their morphology. At the same time, boiling of lysozyme amyloids leads to their irreversible degradation, which occurs at least 5 days after exposure: fibrils that form larger clusters change their secondary structure, and fibrils with a lesser degree of clustering are divided into separate fibers. Obtained data about the factors that change the stability and structure of amyloids can be applied in biotechnology for creating new high-strength nanomaterials on their basis.

scholarly journals Cryo-EM structure of disease-related prion fibrils provides insights into seeding barriers

2021 ◽  
Author(s):  
Qiuye Li ◽  
Christopher P. Jaroniec ◽  
Witold K. Surewicz
Keyword(s):  
High Resolution ◽  
Prion Protein ◽  
Prion Disease ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Protein Aggregates ◽  
Direct Support ◽  
Human Prion Protein ◽  
Structural Insight

One of the least understood aspects of prion diseases is the structure of infectious prion protein aggregates. Here we report a high-resolution cryo-EM structure of amyloid fibrils formed by human prion protein with Y145Stop mutation that is associated with a familial prion disease. This structural insight allows us not only to explain previous biochemical findings, but also provides direct support for the conformational adaptability model of prion transmissibility barriers.

Central Asia: International Relations As A Factor Of Regional Stability And Integration

2020 ◽  
Vol 02 (10) ◽  
pp. 135-140
Author(s):  
B.O. Berdiyev ◽  
Keyword(s):  
International Relations ◽  
Central Asia ◽  
Interethnic Relations ◽  
Regional Stability ◽  
External Influences ◽  
The Stability

The article is devoted to the issues of interethnic relations in Central Asia, the need for integration and cooperation between states, external influences, information impacts on the peoples of the region, border issues, overpopulation, ethnic issues and their impact on the stability of the region.

scholarly journals Temperature-Dependent Structural Variability of Prion Protein Amyloid Fibrils

2021 ◽  
Vol 22 (10) ◽  
pp. 5075
Author(s):  
Mantas Ziaunys ◽  
Andrius Sakalauskas ◽  
Kamile Mikalauskaite ◽  
Ruta Snieckute ◽  
Vytautas Smirnovas
Keyword(s):  
Protein Aggregation ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Morphological Properties ◽  
Large Sample Size ◽  
Structural Variations ◽  
Temperature Dependent ◽  
Protein Fibrils ◽  
Propagation Properties

Prion protein aggregation into amyloid fibrils is associated with the onset and progression of prion diseases—a group of neurodegenerative amyloidoses. The process of such aggregate formation is still not fully understood, especially regarding their polymorphism, an event where the same type of protein forms multiple, conformationally and morphologically distinct structures. Considering that such structural variations can greatly complicate the search for potential antiamyloid compounds, either by having specific propagation properties or stability, it is important to better understand this aggregation event. We have recently reported the ability of prion protein fibrils to obtain at least two distinct conformations under identical conditions, which raised the question if this occurrence is tied to only certain environmental conditions. In this work, we examined a large sample size of prion protein aggregation reactions under a range of temperatures and analyzed the resulting fibril dye-binding, secondary structure and morphological properties. We show that all temperature conditions lead to the formation of more than one fibril type and that this variability may depend on the state of the initial prion protein molecules.

scholarly journals The Ultrastructure of Tissue Damage by Amyloid Fibrils

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4611
Author(s):  
Haruki Koike ◽  
Masahisa Katsuno
Keyword(s):  
Tissue Damage ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Prion Diseases ◽  
Nerve Biopsy ◽  
Al Amyloidosis ◽  
Amyloid Fibril Formation ◽  
Autopsy Specimens ◽  
Fibril Aggregates ◽  
Interfering Rna

Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: 1) reducing or preventing the production of causative proteins; 2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or 3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.

Dynamics and Fluidity of Amyloid Fibrils:  A Model of Fibrous Protein Aggregates

2002 ◽  
Vol 124 (51) ◽  
pp. 15150-15151 ◽  
Author(s):  
Ami S. Lakdawala ◽  
David M. Morgan ◽  
Dennis C. Liotta ◽  
David G. Lynn ◽  
James P. Snyder
Keyword(s):  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Fibrous Protein

Computational analysis of the effect of [Tea][Ms] and [Tea][H2PO4] ionic liquids on the structure and stability of Aβ(17–42) amyloid fibrils

2021 ◽  
Vol 23 (11) ◽  
pp. 6695-6709
Author(s):  
D. Gobbo ◽  
A. Cavalli ◽  
P. Ballone ◽  
A. Benedetto
Keyword(s):  
Ionic Liquid ◽  
Hydrogen Bonding ◽  
Ionic Liquids ◽  
Liquid Water ◽  
Computational Analysis ◽  
Amyloid Fibrils ◽  
Aβ Peptides ◽  
Structure And Stability ◽  
Water Solutions ◽  
Kinetics Of

Tight coordination of peptides by organic anions driven by hydrogen bonding affects the fibrillation kinetics of Aβ peptides in ionic liquid/water solutions.

scholarly journals The Effect of Octapeptide Repeats on Prion Folding and Misfolding

2021 ◽  
Vol 22 (4) ◽  
pp. 1800
Author(s):  
Kun-Hua Yu ◽  
Mei-Yu Huang ◽  
Yi-Ru Lee ◽  
Yu-Kie Lin ◽  
Hau-Ren Chen ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Age Of Onset ◽  
Prion Diseases ◽  
Critical Role ◽  
Threshold Effect ◽  
Central Feature ◽  
Terminal Domain ◽  
Amyloid Aggregates

Misfolding of prion protein (PrP) into amyloid aggregates is the central feature of prion diseases. PrP has an amyloidogenic C-terminal domain with three α-helices and a flexible tail in the N-terminal domain in which multiple octapeptide repeats are present in most mammals. The role of the octapeptides in prion diseases has previously been underestimated because the octapeptides are not located in the amyloidogenic domain. Correlation between the number of octapeptide repeats and age of onset suggests the critical role of octapeptide repeats in prion diseases. In this study, we have investigated four PrP variants without any octapeptides and with 1, 5 and 8 octapeptide repeats. From the comparison of the protein structure and the thermal stability of these proteins, as well as the characterization of amyloids converted from these PrP variants, we found that octapeptide repeats affect both folding and misfolding of PrP creating amyloid fibrils with distinct structures. Deletion of octapeptides forms fewer twisted fibrils and weakens the cytotoxicity. Insertion of octapeptides enhances the formation of typical silk-like fibrils but it does not increase the cytotoxicity. There might be some threshold effect and increasing the number of peptides beyond a certain limit has no further effect on the cell viability, though the reasons are unclear at this stage. Overall, the results of this study elucidate the molecular mechanism of octapeptides at the onset of prion diseases.

scholarly journals PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Allison Kraus ◽  
Gregory J. Raymond ◽  
Brent Race ◽  
Katrina J. Campbell ◽  
Andrew G. Hughson ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Clinical Signs ◽  
Protein Aggregates ◽  
Structural Features ◽  
Spongiform Encephalopathy ◽  
Specific Sequence

ABSTRACT Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro, only some are transmissible and pathogenic in vivo. To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro. Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood. Here we have compared the combined effects of prion seeding and mutations of prion protein (PrP) on the structure and transmission properties of synthetic PrP aggregates. Our results highlight the influence of specific sequence features in the normally unstructured region of PrP that influence the infectious and neuropathogenic properties of PrP-derived aggregates.

Sign in / Sign up

Export Citation Format

Share Document