The Contrasting Effect of Macromolecular Crowding on Amyloid Fibril Formation

Ma, Qi; Fan, Jun-Bao; Zhou, Zheng; Zhou, Bing-Rui; Meng, Sheng-Rong; Hu, Ji-Ying; Chen, Jie; Liang, Yi

doi:10.1371/journal.pone.0036288

Cited by 72 publications

(99 citation statements)

References 48 publications

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“…conditions, PEGs can facilitate or inhibit protein aggregation [21,22]. PEG treatment after traumatic brain injury reduces the accumulation of -amyloid precursor protein in degenerating axons [23].…”

Section: Marta Kotormanamentioning

confidence: 99%

Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of Fibrillation by PEG

Kotormán

Simon

Borics

et al. 2015

PPL

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Abstract:The formation of amyloid-like fibrils was studied by using the well-known serine protease trypsin as a model protein in the presence of ethanol as organic solvent. Trypsin forms amyloid-like fibrils in aqueous ethanol at pH = 7.0. The dye Congo red (CR) was used to detect the presence of amyloid-like fibrils in the samples. The binding of CR to fibrils led to an increase in absorption intensity and a red shift in the absorption band of CR. Thioflavin T (ThT) and 8-anilino-1-naphthalenesulfonic acid (ANS) binding assays were employed to characterize amyloid-like fibril formation. The ThT binding assay revealed that the protein exhibited maximum aggregation in 60% (v/v) ethanol after incubation for 24 h at 24 o C. The ANS binding results indicated that the hydrophobic residues were more exposed to the solvent in the aggregated form of the protein. The effects of polyethylene glycol (PEG) on the formation of amyloid-like fibrils was studied in vitro. The aggregation of trypsin was followed via the kinetics of aggregation, the far-UV circular dichroism (CD) and transmission electron microscopy (TEM) in the presence and absence of PEG. The CD measurements indicated that the protein aggregates have a cross-beta structure in 60% ethanol. TEM revealed that trypsin forms fibrils with a thread-like structure. The inhibitory effect of PEG on the aggregation of trypsin increased with rising PEG concentration. PEG therefore inhibits the formation of amyloid-like fibrils of trypsin in aqueous ethanol.

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Section: Marta Kotormanamentioning

confidence: 99%

Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of Fibrillation by PEG

Kotormán

Simon

Borics

et al. 2015

PPL

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“…3, prion protein is a GPI-anchored cell surface protein and the conversion of PrP from a normal soluble conformation PrP C to its pathogenic conformation PrP Sc is dramatically accelerated by crowded physiological environment containing high concentrations of polysaccharides and collagen. Our data suggested that prion-like proteins associated with neurodegenerative diseases are more inclined to form amyloid fibrils in crowded physiological environments than in dilute solutions [64,66,67]. The 'driving power' for fibrillization of prion-like proteins involves both the formation of an intermolecular or intramolecular disulfide bond and non-covalent interactions such as electrostatic interactions, hydrogen bonds, and hydrophobic interactions, which could be enhanced by crowded physiological environments [66].…”

Section: Prion-like Protein Aggregation In Crowded Physiological Envimentioning

confidence: 81%

“…It is known that in vivo human prion protein and its pathogenic mutants, human Tau protein and its pathogenic mutants, and human SOD1 pathogenic mutants have the tendency to form amyloid deposits in many different kinds of tissue and they are associated with different kinds of neurodegenerative diseases [64]. However, it is hard to distinguish the factors that affect prion-like protein aggregation in vivo because of the interaction network between proteins and proteins, proteins and nucleic acids, and so on.…”

Section: Prion-like Protein Aggregation In Crowded Physiological Envimentioning

confidence: 99%

“…However, it is hard to distinguish the factors that affect prion-like protein aggregation in vivo because of the interaction network between proteins and proteins, proteins and nucleic acids, and so on. Therefore, it is necessary to imitate crowded physiological environments where prion-like protein aggregation takes place by the addition of macromolecular crowding agents in vitro [64][65][66][67]. In macromolecular crowding environments, choosing the right crowders is the key event.…”

Section: Prion-like Protein Aggregation In Crowded Physiological Envimentioning

confidence: 99%

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Recent progress in prion and prion-like protein aggregation

Yi¹,

Xu²,

Chen³

et al. 2013

ABBS

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Prion diseases and prion-like protein misfolding diseases involve the accumulation of abnormally aggregated forms of the normal host proteins, such as prion protein and Tau protein. These proteins are special because of their self-duplicating and transmissible characteristics. Such abnormally aggregated proteins mainly formed in neurons, cause the neurons dysfunction, and finally lead to invariably fatal neurodegenerative diseases. Prion diseases appear not only in animals, such as bovine spongiform encephalopathy in cattle and scrapie in sheep, but also in humans, such as Creutzfeldt -Jacob disease, and even the same prion or prion-like proteins can have many different phenotypes. A lot of biological evidence has suggested that the molecular basis for different strains of prions could be hidden in protein conformations, and the misfolded proteins with conformations different from the normal proteins have been proved to be the main cause for protein aggregation. Crowded physiological environments can be imitated in vitro to study how the misfolding of these proteins leads to the diseases in vivo. In this review, we provide an overview of the existing structural information for prion and prion-like proteins, and discuss the post-translational modifications of prion proteins and the difference between prion and other infectious pathogens. We also discuss what makes a misfolded protein become an infectious agent, and show some examples of prion-like protein aggregation, such as Tau protein aggregation and superoxide dismutase 1 aggregation, as well as some cases of prion-like protein aggregation in crowded physiological environments.

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“…A number of previous studies showed that a few animals such as rabbits exhibit low susceptibility to be infected by the PrP Sc (Vorberg et al, 2003;Khan et al, 2010;Barlow & Rennie, 1976;Fernandez-Funez et al, 2009;Korth et al, 1997;Courageot et al, 2008;Vilette et al, 2001;Nisbet et al, 2010;Wen et al, 2010aWen et al, & 2010bZhou et al, 2011;Ma et al, 2012). Now experimental structural data for rabbit PrP C (RaPrP C ) is available from the Protein Data Bank (PDB bank: http://www.rcsb.org/).…”

Section: The Role Of Prpmentioning

confidence: 99%

A review on the salt bridge ASP177-ARG163 (O–N) of wild-type rabbit prion protein

Zhang

Wang

2016

Journal of Biomolecular Structure and Dynamics

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Abstract:Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elks, humans and mice etc., but rabbits have a low susceptibility to be infected by prion diseases with respect to other species. The stability of rabbit prion protein is due to its highly ordered β2-α2 loop (PLoS One 5(10) e13273 X-ray file of the rabbit prion protein, we can clearly observe this salt bridge. This article analyses the NMR and X-ray structures and gives an answer to the above question: the salt bridge presents at pH 6.5 in the X-ray structure is simply gone at pH 4.5 in the NMR structure is simply due to the different pH values that impact electrostatics at the salt bridge and hence also impact the structures. Moreover, some molecular dynamics simulation results of the X-ray structure are reported in this article to reveal the secrets of the structural stability of rabbit prion protein.

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The Contrasting Effect of Macromolecular Crowding on Amyloid Fibril Formation

Cited by 72 publications

References 48 publications

Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of Fibrillation by PEG

Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of Fibrillation by PEG

Recent progress in prion and prion-like protein aggregation

A review on the salt bridge ASP177-ARG163 (O–N) of wild-type rabbit prion protein

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