A kinetic study of β‐lactoglobulin amyloid fibril formation promoted by urea

Hamada, Daizo; Dobson, Christopher M.

doi:10.1110/ps.0217702

Cited by 256 publications

(191 citation statements)

References 67 publications

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“…ThT has been shown to bind specifically to cross ␤-sheet structures of amyloids (43,44), thus routinely used to monitor amyloid formation kinetics (45)(46)(47)(48). At the beginning of the experiment (0 h), low ThT binding was observed in both samples (SST or SST-Hep) (Fig.…”

Section: Resultsmentioning

confidence: 93%

Elucidating the Role of Disulfide Bond on Amyloid Formation and Fibril Reversibility of Somatostatin-14

Arunagiri

Ranganathan

Dhaked

et al. 2014

Journal of Biological Chemistry

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Background: Peptide/protein hormones are stored as amyloids within endocrine secretory granules. Results: Disulfide bond cleavage enhances conformational dynamics and aggregation kinetics in somatostatin-14, resulting in amyloid fibrils with increased resistance to denaturing conditions and decreased reversibility. Conclusion: Disulfide bond could be a key modulating factor in somatostatin-14 amyloid formation associated with secretory granule biogenesis. Significance: Defective disulfide bonding might cause dysregulation of hormone storage/secretion.

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Section: Resultsmentioning

confidence: 93%

Elucidating the Role of Disulfide Bond on Amyloid Formation and Fibril Reversibility of Somatostatin-14

Arunagiri

Ranganathan

Dhaked

et al. 2014

Journal of Biological Chemistry

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“…The whey protein β-lactoglobulin forms amyloid-like fibrils under several different conditions, including high concentrations of urea (20), in the presence of alcohols (21), and at low pH and elevated temperature (5,22). At low pH and high temperature, the fibrillation proceeds through hydrolysis of the protein into smaller peptide fragments and some of these peptides spontaneously assemble into PNFs (23).…”

Section: Resultsmentioning

confidence: 99%

Flow-assisted assembly of nanostructured protein microfibers

Kamada

Mittal

Söderberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

115

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Some of the most remarkable materials in nature are made from proteins. The properties of these materials are closely connected to the hierarchical assembly of the protein building blocks. In this perspective, amyloid-like protein nanofibrils (PNFs) have emerged as a promising foundation for the synthesis of novel bio-based materials for a variety of applications. Whereas recent advances have revealed the molecular structure of PNFs, the mechanisms associated with fibril-fibril interactions and their assembly into macroscale structures remain largely unexplored. Here, we show that whey PNFs can be assembled into microfibers using a flow-focusing approach and without the addition of plasticizers or cross-linkers. Microfocus small-angle X-ray scattering allows us to monitor the fibril orientation in the microchannel and compare the assembly processes of PNFs of distinct morphologies. We find that the strongest fiber is obtained with a sufficient balance between ordered nanostructure and fibril entanglement. The results provide insights in the behavior of protein nanostructures under laminar flow conditions and their assembly mechanism into hierarchical macroscopic structures.protein nanofibrils | amyloid | hierarchical assembly | flow focusing | small-angle X-ray scattering P roteins are widely used in nature to create high-performance materials that can have both extraordinary mechanical properties (similar to muscles, silks) and sophisticated functionalities (e.g., adhesion, biological signaling) (1). The characteristics of these materials are intimately connected to the hierarchical assembly of the protein building blocks with well-defined organization at all structural levels (2). Improved knowledge about how to control the assembly of protein molecules into higher-order structures would open the possibilities to create novel bio-based materials for a variety of applications. In this perspective, the ability of protein molecules to undergo nonnative self-assembly into protein nanofibrils (PNFs) with highly organized supramolecular structures is of significant interest (3). The formation of PNFs was initially observed in association with diseases, such as Alzheimer's and Parkinson's diseases, and type II diabetes, where human organs are impaired by fibrous protein inclusions referred to as amyloid (4). However, several non-disease-related proteins have also been shown to form amyloid-like fibrils, e.g., the bovine whey protein β-lactoglobulin (5), hen-egg lysozyme (6), and soybean proteins (7). The unique fibrous structures of PNFs have the potential for being the building block of protein-based nanomaterials and to be used as scaffolds for applications such as tissue engineering, drug delivery systems, and biosensors (3). PNFs are characterized by intermolecular β-sheet structures, where the peptide backbones are oriented perpendicularly to the fibril axis and connected through a network of hydrogen bonds (4,8). This provides them with stiffness equivalent to silk and strength comparable to steel (2, 8). Moreo...

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“…Both α-LA and β-LG form fibrils over a wide range of destabilizing conditions (Goers et al, 2002;Hamada and Dobson, 2002;Arnaudov et al, 2003;de Laureto et al, 2005). Similarly, BSA forms amyloid fibril-like structures at 85°C (Pearce et al, 2007).…”

Section: Casein Amyloid Fibrilsmentioning

confidence: 99%

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

Holt

Carver

Ecroyd

et al. 2013

Journal of Dairy Science

386

240

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A typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins. The ability to suppress amyloid fibril formation by forming an alternative amorphous aggregate is also not unique to caseins and underlies the action of molecular chaperones such as the small heat-shock proteins. The open structure of the protein matrix of casein micelles is fragile and easily perturbed by changes in its environment. Perturbations can cause the polypeptide chains to segregate into regions of greater and lesser density. As a result, the reliable determination of the native structure of casein micelles continues to be extremely challenging. The biological functions of caseins, such as their chaperone activity, are determined by their composition and flexible conformation and by how the casein polypeptide chains interact with each other. These same properties determine how caseins behave in the manufacture of many dairy products and how they can be used as functional ingredients in other foods. aBStraCtA typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosp...

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A kinetic study of β‐lactoglobulin amyloid fibril formation promoted by urea

Cited by 256 publications

References 67 publications

Elucidating the Role of Disulfide Bond on Amyloid Formation and Fibril Reversibility of Somatostatin-14

Elucidating the Role of Disulfide Bond on Amyloid Formation and Fibril Reversibility of Somatostatin-14

Flow-assisted assembly of nanostructured protein microfibers

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

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