Common Fibril Structures Imply Systemically Conserved Protein Misfolding Pathways In Vivo

Annamalai, Karthikeyan; Liberta, Falk; Vielberg, M.-T.; Close, William; Lilie, Hauke; Gührs, Karl‐Heinz; Schierhorn, Angelika; Koehler, Rolf; Schmidt, Andreas; Haupt, Christian; Hegenbart, Ute; Schönland, Stefan; Schmidt, Matthias; Groll, M.; Fändrich, Marcus

doi:10.1002/ange.201701761

Cited by 14 publications

(14 citation statements)

References 21 publications

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“…It is also seen when analysing amyloid fibrils extracted from patients or animal diseased with amyloidosis. A comparative analysis of fibrils extracted from different forms of amyloidosis revealed polymorphic fibril morphologies based on electron microscopy, and this result was independent of the type of amyloidosis analysed, the amyloid‐forming protein, and the organ involved in the amyloid deposition . Changing the conditions of fibril formation in vitro can alter the distribution of fibril polymorphs present in a sample .…”

Section: Amyloid Fibril Polymorphismmentioning

confidence: 99%

“…Similar to observations made with fibrils extracted from systemic ATTR amyloidosis, it was found that different patients were associated with different ensembles of fibril morphologies. Interestingly, however, within the same patient, consistent fibril morphologies were seen in the different tissues (heart muscle, heart fat and abdominal fat) . Detailed fibril structures by cryo‐EM are currently available for a 12‐residue peptide fragment of an amyloidogenic light chain .…”

Section: Light Chainsmentioning

confidence: 99%

“…In all animals, multiple fibril morphologies were found per individual. Interestingly, comparison of the spleens and liver of the same animal revealed the same fibril morphologies to be present in both organs . In contrast to different cases of human AL amyloidosis, each being associated with a genetically different fibril precursor protein, different AA amyloidotic mice showed the same polymorphs .…”

Section: Saamentioning

confidence: 99%

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Amyloid fibril polymorphism: a challenge for molecular imaging and therapy

et al. 2018

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Section: Amyloid Fibril Polymorphismmentioning

confidence: 99%

Section: Light Chainsmentioning

confidence: 99%

Section: Saamentioning

confidence: 99%

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Amyloid fibril polymorphism: a challenge for molecular imaging and therapy

et al. 2018

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“…Because of protein aggregation, fibrillar aggregates get deposited in the specific body tissues. 3 Amyloid fibers formed from different proteins share some common features as these are rich in β structures where β-sheets are perpendicularly arranged to the fibrillar axis. 4 The organization of fibrils, kinetics, and their overall stability is highly governed by the amino acid sequence of proteins and the surrounding environmental conditions.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Glycation-Induced Aggregation of Human Serum Albumin by Organic–Inorganic Hybrid Nanocomposites of Iron Oxide-Functionalized Nanocellulose

Singla¹,

Abidi²,

Dar³

et al. 2019

ACS Omega

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Protein aggregation leads to the transformation of proteins from their soluble form to the insoluble amyloid fibrils and these aggregates get deposited in the specific body tissues, accounting for various diseases. To prevent such an aggregation, organic–inorganic hybrid nanocomposites of iron oxide nanoparticle (NP, ∼6.5–7.0 nm)-conjugated cellulose nanocrystals (CNCs) isolated from Syzygium cumini (SC) and Pinus roxburghii (PR) were chemically synthesized. Transmission electron microscopy (TEM) images of the nanocomposites suggested that the in situ-synthesized iron oxide NPs were bound to the CNC surface in a uniform and regular fashion. The ThT fluorescence assay together with 8-anilino-1-naphthalenesulfonic acid, Congo Red, and CD studies suggested that short fiber-based SC nanocomposites showed better inhibition as well as dissociation of human serum albumin aggregates. The TEM and fluorescence microscopy studies supported similar observations. Native polyacrylamide gel electrophoresis results documented dissociation of higher protein aggregates in the presence of the developed nanocomposite. Interestingly, the dissociated proteins retained their biological function by maintaining a high amount of α-helix content. The in vitro studies with HEK-293 cells suggested that the developed nanocomposite reduces aggregation-induced cytotoxicity by intracellular reactive oxygen species scavenging and maintaining the Ca2+ ion-channel. These results indicated that the hybrid organic–inorganic nanocomposite, with simultaneous sites for hydrophobic and hydrophilic interactions, tends to provide a larger surface area for nanocomposite–protein interactions, which ultimately disfavors the nucleation step for fibrillation for protein aggregates.

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“…The amyloid fibril is a type of insoluble protein that aggregate with a specific secondary structure. [3][4][5][8][9][10]. Lysozyme is not associated with any known amyloid diseases; however, it shares similar morphological features with amyloids from disease associated proteins.…”

mentioning

confidence: 99%

Do carbon nanotubes inhibit or promote amyloid fibrils formation?

Olenchuk

Gnatyuk

Dovbeshko

et al. 2019

Biophysical Bulletin

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Objectives: The purpose of the work was to study the effect of carbon nanotubes on the formation of fibril structures in lysozyme at room temperature under different pH values. Materials and methods: For the preparation of the samples, hen egg-white lysozyme protein (HEWL, Fluka), as well as single-walled (SWCNT, Sigma-Aldrich) and multi-walled (MWCNT, OOO TM “Spetsmash”, Kyiv, Ukraine) carbon nanotubes were used. Used techniques: IR-Fourier Absorption Spectroscopy; confocal microscopy. Results: In this paper, the study of molecular mechanisms of interaction of lysozyme with carbon nanotubes by vibrational spectroscopy was carried out and a conformational analysis of the formed complexes was performed. It is shown that carbon nanotubes can affect the structure of lysozyme even at room temperature and normal pH values, as evidenced by conformational changes in lysozyme due to interaction with carbon nanotubes. Complexes which are formed as a result of such interaction, have characteristic features of amyloid fibrillar structures. It reveals one of possible mechanisms of carbon nanotubes cytotoxicity. On the other hand, such a technique can be introduced to obtain model amyloid fibrils for further study. Conclusion: The method of vibtarional spectroscopy has shown that carbon nanotubes can influence the structure of lysozyme, as it is shown by the conformational analysis of the absorption band Amide I. After the interaction of lysozyme with CNT, an increase in the contribution of antiparallel β-conformation in the structure of lysozyme is observed, and the contribution of the α-helix conformation is reduced, which are characteristic features in the formation of fibrillar structures. The possibility of amyloid fibril formation without the use of high temperatures at different pH values with the interaction of lysozyme and carbon nanotubes, which can be applied as a method for obtaining the model amyloid fibrils, is shown.

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Common Fibril Structures Imply Systemically Conserved Protein Misfolding Pathways In Vivo

Cited by 14 publications

References 21 publications

Amyloid fibril polymorphism: a challenge for molecular imaging and therapy

Amyloid fibril polymorphism: a challenge for molecular imaging and therapy

Inhibition of Glycation-Induced Aggregation of Human Serum Albumin by Organic–Inorganic Hybrid Nanocomposites of Iron Oxide-Functionalized Nanocellulose

Do carbon nanotubes inhibit or promote amyloid fibrils formation?

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