scholarly journals Nucleophilic Regulation of the Formation of Melanin-like Species by Amyloid Fibers

ACS Omega ◽  
2021 ◽  
Author(s):  
Daehong Ha ◽  
Kyungtae Kang
Keyword(s):  
Amyloid Fibers

A Chemical Perspective to the Anti-Amyloid Action of Compounds and a Nanoparticle Based Assay for Screening Amyloid Inhibitors

2020 ◽  
Author(s):  
Nidhi Gour ◽  
Bharti Koshti
Keyword(s):  
Memory Loss ◽  
Cost Effective ◽  
Structural Motif ◽  
Rapid Screening ◽  
Stacking Interactions ◽  
Aromatic Rings ◽  
Amyloid Fibers ◽  
Aromatic Stacking ◽  
Cost Effective Technique ◽  
The Brain

Aggregation of amyloid beeta 1-42 (Aβ<sub>42</sub>) peptide causes the formation of clustered deposits knows as amyloid plaques in the brain which leads to neuronal dysfunction and memory loss and associated with many neurological disorders including Alzheimer’s and Parkinson’s. Aβ<sub>42</sub> has core structural motif with phenylalanine at the 19 and 20 positions. The diphenylalanine (FF) residue plays a crucial role in the formation of amyloid fibers and serves as model peptide for studying Aβ<sub>42 </sub>aggregation. FF self-assembles to well-ordered tubular morphology via aromatic pi-pi stackings. Our studies, suggest that the aromatic rings present in the anti-amyloidogenic compounds may interact with the pi-pi stacking interactions present in the FF. Even the compounds which do not have aromatic rings, like cyclodextrin and cucurbituril show anti-amyloid property due to the binding of aromatic ring inside the guest cavity. Hence, our studies also suggest that compounds which may have a functional moiety capable of interacting with the aromatic stacking interactions might be tested for their anti-amyloidogenic properties. Further, in this manuscript, we have proposed two novel nanoparticle based assays for the rapid screening of amyloid inhibitors. In the first assay, interaction between biotin-tagged FF peptide and the streptavidin labelled gold nanoparticles (s-AuNPs) were used. In another assay, thiol-Au interactions were used to develop an assay for detection of amyloid inhibitors. It is envisaged that the proposed analytical method will provide a simple, facile and cost effective technique for the screening of amyloid inhibitors and may be of immense practical implications to find the therapeutic remedies for the diseases associated with the protein aggregation.

scholarly journals Distinct Subregions of Swi1 Manifest Striking Differences in Prion Transmission and SWI/SNF Function

2010 ◽  
Vol 30 (19) ◽  
pp. 4644-4655 ◽  
Author(s):  
Zhiqiang Du ◽  
Emily T. Crow ◽  
Hyun Seok Kang ◽  
Liming Li
Keyword(s):  
Chromatin Remodeling ◽  
De Novo ◽  
Amino Acid Residues ◽  
Coding Region ◽  
Conformational Switch ◽  
Amyloid Fibers ◽  
Aggregation Pattern ◽  
Prion Transmission ◽  
Shed Light

ABSTRACT We have recently reported that the yeast chromatin-remodeling factor Swi1 can exist as a prion, [SWI +], demonstrating a link between prionogenesis and global transcriptional regulation. To shed light on how the Swi1 conformational switch influences Swi1 function and to define the sequence and structural requirements for [SWI +] formation and propagation, we functionally dissected the Swi1 molecule. We show here that the [SWI +] prion features are solely attributable to the first 327 amino acid residues (N), a region that is asparagine rich. N was aggregated in [SWI+ ] cells but diffuse in [swi− ] cells; chromosomal deletion of the N-coding region resulted in [SWI +] loss, and recombinant N peptide was able to form infectious amyloid fibers in vitro, enabling [SWI +] de novo formation through a simple transformation. Although the glutamine-rich middle region (Q) was not sufficient to aggregate in [SWI +] cells or essential for SWI/SNF function, it significantly modified the Swi1 aggregation pattern and Swi1 function. We also show that excessive Swi1 incurred Li+/Na+ sensitivity and that the N/Q regions are important for this gain of sensitivity. Taken together, our results provide the final proof of “protein-only” transmission of [SWI +] and demonstrate that the widely distributed “dispensable” glutamine/asparagine-rich regions/motifs might have important and divergent biological functions.

Amyloid fibers deriving from the aromatic core of C-terminal domain of nucleophosmin 1

2019 ◽  
Vol 122 ◽  
pp. 517-525 ◽  
Author(s):  
Sara La Manna ◽  
Valentina Roviello ◽  
Pasqualina Liana Scognamiglio ◽  
Carlo Diaferia ◽  
Cinzia Giannini ◽  
...  
Keyword(s):  
Amyloid Fibers ◽  
Terminal Domain

scholarly journals FRET-based Tau seeding assay does not represent prion-like templated assembly of Tau filaments

2020 ◽  
Author(s):  
Senthilvelrajan Kaniyappan ◽  
Katharina Tepper ◽  
Jacek Biernat ◽  
RamReddy Chandupatla ◽  
Sabrina Hübschmann ◽  
...  
Keyword(s):  
Recipient Cell ◽  
Pathological State ◽  
Tau Pathology ◽  
Amyloid Fibers ◽  
Force Microscopy ◽  
Atomic Force ◽  
Transmission Electron ◽  
Repeat Domain ◽  
Scanning Transmission ◽  
Tau Aggregation

Abstract Tau aggregation into amyloid fibers based on the cross-beta structure is a hallmark of several Tauopathies, including Alzheimer Disease (AD). Trans-cellular propagation of Tau with pathological conformation has been suggested as a key disease mechanism. This is thought to cause the spreading of Tau pathology in AD by templated conversion of naive Tau in recipient cells into a pathological state, followed by assembly of pathological Tau fibers, similar to the mechanism of nucleated polymerization proposed for prion pathogenesis. In cell cultures, the process is often monitored by a FRET assay where the recipient cell expresses the Tau repeat domain (TauRD) with a pro-aggregant mutation, fused to GFP-based FRET pairs. Since the size of the reporter GFP (barrel of ~3nm x 4nm) is ~7 times larger than the β-strand distance (0.47nm), this points to a potential steric clash. Hence, we investigated the influence of the GFP tag on Tau or TauRD aggregation. Using biophysical methods (light scattering, atomic force microscopy (AFM), and scanning-transmission electron microscopy (STEM)), we found that the assembly of TauRD-GFP was severely inhibited and incompatible with that of Alzheimer filaments. These observations argue against the hypothesis that the propagation of Tau pathology in AD is caused by the prion-like templated aggregation of Tau protein, transmitted via cell-to-cell spreading of Tau. Thus, even though the observed local increase of FRET in recipient cells may be a valid hallmark of a pathological reaction, our data argue that it is caused a process distinct from assembly of TauRD filaments.

Formation of Amyloid Fibers Triggered by Phosphatidylserine-Containing Membranes†

Biochemistry ◽  
2004 ◽  
Vol 43 (32) ◽  
pp. 10302-10307 ◽  
Author(s):  
Hongxia Zhao ◽  
Esa K. J. Tuominen ◽  
Paavo K. J. Kinnunen
Keyword(s):  
Amyloid Fibers

scholarly journals Genetically encoded self-assembly of large amyloid fibers

2014 ◽  
Vol 2 (4) ◽  
pp. 560-566 ◽  
Author(s):  
D. M. Ridgley ◽  
B. G. Freedman ◽  
P. W. Lee ◽  
J. R. Barone
Keyword(s):  
Self Assembly ◽  
Experimental Results ◽  
Amyloid Fibers

Experimental results demonstrate that large amyloid fibers can be engineered at the DNA level, spanning four orders of magnitude.

scholarly journals Structural basis for the disaggregase activity and regulation of Hsp104

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Alexander Heuck ◽  
Sonja Schitter-Sollner ◽  
Marcin Józef Suskiewicz ◽  
Robert Kurzbauer ◽  
Juliane Kley ◽  
...  
Keyword(s):  
General Model ◽  
Coiled Coil ◽  
Cellular Proteins ◽  
Structural Basis ◽  
Collateral Damage ◽  
Amyloid Fibers ◽  
Toxic Protein ◽  
Native Proteins ◽  
Chaetomium Thermophilum ◽  
Mechanical Linkage

The Hsp104 disaggregase is a two-ring ATPase machine that rescues various forms of non-native proteins including the highly resistant amyloid fibers. The structural-mechanistic underpinnings of how the recovery of toxic protein aggregates is promoted and how this potent unfolding activity is prevented from doing collateral damage to cellular proteins are not well understood. Here, we present structural and biochemical data revealing the organization of Hsp104 from Chaetomium thermophilum at 3.7 Å resolution. We show that the coiled-coil domains encircling the disaggregase constitute a ‘restraint mask’ that sterically controls the mobility and thus the unfolding activity of the ATPase modules. In addition, we identify a mechanical linkage that coordinates the activity of the two ATPase rings and accounts for the high unfolding potential of Hsp104. Based on these findings, we propose a general model for how Hsp104 and related chaperones operate and are kept under control until recruited to appropriate substrates.

scholarly journals Gels of Amyloid Fibers

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 210 ◽  
Author(s):  
Ruizhi Wang ◽  
Xiaojing Yang ◽  
Lingwen Cui ◽  
Hang Yin ◽  
Shaohua Xu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Atomic Force Microscopy ◽  
Melting Point ◽  
Protein Concentration ◽  
Size Exclusion ◽  
Amyloid Fibers ◽  
Force Microscopy ◽  
Atomic Force ◽  
3D Network

Protein self-assembly and formation of amyloid fibers is an early event of numerous human diseases. Continuous aggregation of amyloid fibers in vitro produces biogels, which led us to suspect that amyloid plaques and neurofibrillary tangles in Alzheimer’s disease are of biogels in nature. We applied atomic force microscopy, size exclusion chromatography, and differential scanning calorimetry to elucidate the gel’s structure, kinetics of gel formation, and melting point. We found that (1) lysozyme gelation occurs when the protein concentration is above 5 mg/mL; (2) nonfibrous protein concentration decreases and plateaus after three days of gel synthesis reaction; (3) colloidal lysozyme aggregates are detectable by both atomic force microscopy (AFM) and fast protein liquid chromatography (FPLC); (4) the gels are a three-dimensional (3D) network crosslinked by fibers coiling around each other; (5) the gels have a high melting point at around around 110 °C, which is weakly dependent on protein concentration; (6) the gels are conductive under an electric field, and (7) they form faster in the presence than in the absence of salt in the reaction buffer. The potential role of the gels formed by amyloid fibers in amyloidosis, particularly in Alzheimer’s disease was thoroughly discussed, as gels with increased viscosity, are known to restrict bulk flow and then circulation of ions and molecules.

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