Different conditions of fibrillogenesis cause polymorphism of lysozyme amyloid fibrils

Sulatskaya, Anna I.; Rodina, Natalia P.; Povarova, Olga I.; Kuznetsova, Irina M.; Turoverov, Konstantin K.

doi:10.1016/j.molstruc.2016.10.037

Cited by 28 publications

(44 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lysozyme (ALys amyloidosis) and beta-2-microglobulin (DRA), as proteins with significantly different secondary and tertiary structures and stability, were chosen by us as target proteins. Amyloid fibrils formed from these proteins were prepared by previously developed approaches [ 42 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

“…Based on the literature data, the acidic conditions of fibrillogenesis were successfully applied for preparation of lysozyme amyloid fibrils with a relatively low tendency to clustering (see Materials and methods) [ 43 ]. The prepared fibrils were transferred into a buffer with pH 7.4, and their stability was monitored during the experiment.…”

Section: Resultsmentioning

confidence: 99%

“…To find out whether the effect of alpha-B-crystallin on fibrils at acidic pH depends on the amino acid sequence of an amyloidogenic protein, a similar experiment in the same conditions was carried out with amyloid fibrils prepared from lysozyme by the special protocol [ 43 ]. As we expected, the effect of alpha-B-crystallin on lysozyme amyloid fibrils at acidic pH was similar to its effect on beta-2-microglobulin amyloid fibrils under the same conditions.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity

Stepanenko

Sulatsky

Михайлова

et al. 2020

IJMS

View full text Add to dashboard Cite

Given the ability of molecular chaperones and chaperone-like proteins to inhibit the formation of pathological amyloid fibrils, the chaperone-based therapy of amyloidosis has recently been proposed. However, since these diseases are often diagnosed at the stages when a large amount of amyloids is already accumulated in the patient’s body, in this work we pay attention to the undeservedly poorly studied problem of chaperone and chaperone-like proteins’ effect on mature amyloid fibrils. We showed that a heat shock protein alpha-B-crystallin, which is capable of inhibiting fibrillogenesis and is found in large quantities as a part of amyloid plaques, can induce degradation of mature amyloids by two different mechanisms. Under physiological conditions, alpha-B-crystallin induces fluffing and unweaving of amyloid fibrils, which leads to a partial decrease in their structural ordering without lowering their stability and can increase their cytotoxicity. We found a higher correlation between the rate and effectiveness of amyloids degradation with the size of fibrils clusters rather than with amino acid sequence of amyloidogenic protein. Some external effects (such as an increase in medium acidity) can lead to a change in the mechanism of fibrils degradation induced by alpha-B-crystallin: amyloid fibers are fragmented without changing their secondary structure and properties. According to recent data, fibrils cutting can lead to the generation of seeds for new bona fide amyloid fibrils and accelerate the accumulation of amyloids, as well as enhance the ability of fibrils to disrupt membranes and to reduce cell viability. Our results emphasize the need to test the chaperone effect not only on fibrillogenesis, but also on the mature amyloid fibrils, including stress conditions, in order to avoid undesirable disease progression during chaperone-based therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity

Stepanenko

Sulatsky

Михайлова

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…We tried to check whether a change in the secondary structure and morphology of amyloid fibrils (while the primary sequence of the amyloidogenic protein is unchanged) affects ANS binding and its effect on amyloids. To change the structure of aggregates formed from insulin and lysozyme, their fibrillogenesis was induced under altered conditions: proteins were dissolved in a buffer with extremely acidic pH (pH 2) in the presence of NaCl and incubated at a temperature of 37°C [31]. After the formation of mature amyloid fibrils, they were transferred to distilled water, and their stability was experimentally confirmed.…”

Section: A Change In the Secondary Structure And Morphology Of Amyloimentioning

confidence: 99%

“…ThT does not interact with globular proteins in a native state (other than with acetylcholinesterase [24] and serum albumins [25,26]), with molten globule and unfolded states or amorphous aggregates of proteins. Due to its unique properties, ThT is a sensitive tool for diagnostics of amyloid fibrils formation, studying the kinetics of fibrillogenesis, and more recently for the study their structure [27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Effect of the fluorescent probes ThT and ANS on the mature amyloid fibrils

Sulatsky

Sulatskaya

Povarova

et al. 2020

Prion

View full text Add to dashboard Cite

Fluorescent probes thioflavin T (ThT) and 1-anilino-8-naphthalene sulfonate (ANS) are widely used to study amyloid fibrils that accumulate in the body of patients with serious diseases, such as Alzheimer's, Parkinson's, prion diseases, etc. However, the possible effect of these probes on amyloid fibrils is not well understood. In this work, we investigated the photophysical characteristics, structure, and morphology of mature amyloid fibrils formed from two model proteins, insulin and lysozyme, in the presence of ThT and ANS. It turned out that ANS affects the secondary structure of amyloids (shown for fibrils formed from insulin and lysozyme) and their fibers clusterization (valid for lysozyme fibrils), while ThT has no such effects. These results confirm the differences in the mechanisms of these dyes interaction with amyloid fibrils. Observed effect of ANS was explained by the electrostatic interactions between the dye molecule and cationic groups of amyloid-forming proteins (unlike hydrophobic binding of ThT) that induce amyloids conformational changes. This interaction leads to weakening repulsion between positive charges of amyloid fibrils and can promote their clusterization. It was shown that when fibrillogenesis conditions and, consequently, fibrils structure is changing, as well as during defragmentation of amyloids by ultrasonication, the influence of ANS to amyloids does not change, which indicates the universality of the detected effects. Based on the obtained results, it was concluded that ANS should be used cautiously for the study of amyloid fibrils, since this fluorescence probe have a direct effect on the object of study.

show abstract

Investigating lysozyme amyloid fibril formation and structural variability dependence on its initial folding state under different pH conditions

Ziaunys,

Mikalauskaite,

Sakalauskas

et al. 2024

Protein Science

View full text Add to dashboard Cite

Protein fibril formation and accumulation is associated with dozens of amyloidoses, including the widespread and yet incurable Alzheimer's and Parkinson's diseases. Currently, there are still several aspects of amyloid aggregation that are not fully understood, which negatively contributes to the development of disease‐altering drugs and treatments. One factor which requires a more in‐depth analysis is the effect of the environment on both the initial state of amyloidogenic proteins, as well their aggregation process and resulting fibril characteristics. In this work, we examine how lysozyme's folding state influences its amyloid formation kinetics and resulting aggregate structural characteristics under several different pH conditions, ranging from acidic to neutral. We demonstrate that both the initial state of the protein, as well as the solution's pH value have a significant combined effect on the variability of the resulting aggregate secondary structures, as well as their stabilities, interactions with amyloid‐specific dye molecules and self‐replication properties.This article is protected by copyright. All rights reserved.

show abstract

Different conditions of fibrillogenesis cause polymorphism of lysozyme amyloid fibrils

Cited by 28 publications

References 48 publications

Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity

Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity

Effect of the fluorescent probes ThT and ANS on the mature amyloid fibrils

Investigating lysozyme amyloid fibril formation and structural variability dependence on its initial folding state under different pH conditions

Contact Info

Product

Resources

About