Catalytic activity of copper ions in the amyloid fibrillation of β-lactoglobulin

Zappone, Bruno; Santo, Maria P. De; Labate, Cristina; Rizzuti, Bruno; Guzzi, Rita

doi:10.1039/c2sm27408f

Cited by 26 publications

(30 citation statements)

References 48 publications

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“…34 EPR studies have shown that Cu 2+ does not bind to βLG in both the native and denaturated protein state. 22 Likewise, the EPR spectrum of freshly prepared βLG/Fe 3+ sample was very similar to the corresponding protein-free FeCl 3 solution (compare lines a and c in Figure 7), indicating that iron cations did not bind to βLG in the native state. In contrast, the resonance line became sharper after incubation of the sample, (ΔH pp reduces to 5.7 mT), clearly indicating that iron ions did bind to βLG in the aggregate state.…”

Section: ■ Resultsmentioning

confidence: 78%

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Ferric Ions Inhibit the Amyloid Fibrillation of β-Lactoglobulin at High Temperature

et al. 2015

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The energetics of amyloid fibrillar aggregation of β-lactoglobulin (βLG) following incubation at high temperature and acid pH was studied by differential scanning calorimetry in the presence of Cu(2+) or Fe(3+) cations, and without any metal. Cu(2+) and metal-free protein solutions showed a distinct exothermic response that disappeared almost completely when the Fe(3+) molar concentration was ten times greater than the βLG concentration. Thioflavin T fluorescence studies in solution and atomic force microscopy analysis of the deposit left on flat mica substrates by heat-incubated βLG solutions correlated the absence of exothermic response of Fe(3+)-βLG solutions with a lack of fibril production. In contrast, abundant fibril deposits were observed for Cu(2+)-βLG solutions, with a rich polymorphism of multistrand fibrillar structures. Electron paramagnetic resonance revealed that Fe(3+) permanently binds to βLG in the aggregate state whereas Cu(2+) plays a catalytic role without binding to the protein. We propose that Fe(3+) inhibits fibril production after binding to a key region of the protein sequence, possibly interfering with the nucleation step of the fibrillation process and opening a nonfibrillar aggregation pathway. These findings suggest that transition metal ions can be utilized to effectively modulate protein self-assembly into a variety of structures with distinct morphologies at the nanoscale level.

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Section: ■ Resultsmentioning

confidence: 78%

“…The area under the C p peak, representing the enthalpy of the transition, decreased from 351 to 339 kJ mol −1 (±1 kJ mol −1 ), as previously reported. 22 Furthermore, ΔC p was reduced to about 7 kJ mol −1°C −1 compared to metal-free solutions, suggesting a lower internal packing density of the βLG molecule.…”

Section: ■ Resultsmentioning

confidence: 99%

Ferric Ions Inhibit the Amyloid Fibrillation of β-Lactoglobulin at High Temperature

et al. 2015

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“…Both glycerol and sorbitol decrease the rate of β-LG selfassembly, but do not affect fibril morphology (Dave, Loveday, Anema, Jameson, & Singh, 2014b). Although copper ions (Cu 2+ ) significantly increase the rate of β-LG fibril nucleation without altering fibril morphology (Zappone, De Santo, Labate, Rizzuti, & Guzzi, 2013), ferric ions (Fe 3+ ) inhibit its fibrillation at high temperature (Guzzi, Rizzuti, Labate, Zappone, & De Santo, 2015). Preformed β-LG AFs reduce ferric to ferrous (Fe 2+ ) ions better than native β-LG but less effective than its nonfibril peptides.…”

Section: Duckermentioning

confidence: 99%

Conditions Governing Food Protein Amyloid Fibril Formation. Part II: Milk and Legume Proteins

Lambrecht

Jansens

Rombouts

et al. 2019

Comp Rev Food Sci Food Safe

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Both intrinsic and extrinsic factors impact amyloid formation of food proteins. We here review the impact of various conditions and food constituents on amyloid fibrillation of milk and legume proteins. Much less is known about casein and legume protein amyloid‐like fibril formation than about that of whey proteins such as β‐lactoglobulin, α‐lactalbumin, and bovine serum albumin. Proteins of both sources are often studied after heating under strong acidic (pH < 3) conditions. The latter induces changes in protein conformation and often peptide hydrolysis. At higher pH values, alcohols, chaotropic and/or reducing agents induce the conformational changes required to enhance fibrillation. Different types of food proteins can impact each other's fibrillation. Also, the presence of other food constituents can enhance or reduce it. No general conclusions on the mechanisms or impact of different food constituents on food proteins can be made. Optimal conditions for AF formation, that is, heating for several days at low pH, are rare in food processing. However, this does not exclude the possibility of AF formation in food products. For example, slow cooking of hydrolyzed proteins may enhance it. Future research should focus on the prevalence of AFs in complex food systems or model systems relevant for food processing.

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“…Food-derived amyloids have outstanding stiffness and a broad availability of functional groups on their surfaces [ 141 ] without exhibiting toxicity. Moreover, some food-derived proteins fibrilize in the presence of transition metals and heating at low pH, e.g., β-lactoglobulin fibrilizes in the presence of Cu(II) and Fe(III) ions [ 142 , 143 ]. Thermal denaturation leads to the exposure of hydrophobic residues, which increases hydrophobic attraction that overcomes electrostatic repulsion, and triggers the aggregation of amorphous aggregates.…”

Section: Functional Metal/amyloid Complexesmentioning

confidence: 99%

“What Doesn’t Kill You Makes You Stronger”: Future Applications of Amyloid Aggregates in Biomedicine

et al. 2020

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Amyloid proteins are linked to the pathogenesis of several diseases including Alzheimer’s disease, but at the same time a range of functional amyloids are physiologically important in humans. Although the disease pathogenies have been associated with protein aggregation, the mechanisms and factors that lead to protein aggregation are not completely understood. Paradoxically, unique characteristics of amyloids provide new opportunities for engineering innovative materials with biomedical applications. In this review, we discuss not only outstanding advances in biomedical applications of amyloid peptides, but also the mechanism of amyloid aggregation, factors affecting the process, and core sequences driving the aggregation. We aim with this review to provide a useful manual for those who engineer amyloids for innovative medicine solutions.

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Catalytic activity of copper ions in the amyloid fibrillation of β-lactoglobulin

Cited by 26 publications

References 48 publications

Ferric Ions Inhibit the Amyloid Fibrillation of β-Lactoglobulin at High Temperature

Ferric Ions Inhibit the Amyloid Fibrillation of β-Lactoglobulin at High Temperature

Conditions Governing Food Protein Amyloid Fibril Formation. Part II: Milk and Legume Proteins

“What Doesn’t Kill You Makes You Stronger”: Future Applications of Amyloid Aggregates in Biomedicine

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