pH driven fibrillar aggregation of the super-sweet protein Y65R-MNEI: A step-by-step structural analysis

Pica, Andrea; Leone, Serena; Girolamo, Rocco Di; Donnarumma, Federica; Emendato, Alessandro; Rega, Michele F.; Merlino, Antonello; Picone, Delia

doi:10.1016/j.bbagen.2017.12.012

Cited by 14 publications

(5 citation statements)

References 54 publications

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“…Thioflavin T (ThT) binding assay was employed; it is frequently used to analyze the kinetic of the self-recognition process associated with amyloid fibers formation [51].…”

Section: Resultsmentioning

confidence: 99%

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

Florio

Malfitano

Somma

et al. 2019

IJMS

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Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties.

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“…Thioflavin T (ThT) binding assay was employed; it is frequently used to analyze the kinetic of the self-recognition process associated with amyloid fibers formation [51].…”

Section: Resultsmentioning

confidence: 99%

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

Florio

Malfitano

Somma

et al. 2019

IJMS

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“…The RNase A self-association occurring through the 3D-DS mechanism and the mutations favoring this event have been deeply studied in the recent past [2,4,6,[8][9][10]12,24,32,44]. Notably, 3D-DS is shared by several amyloidogenic proteins [17,18,44] that form toxic vs. non-toxic oligomers as a function of the environmental conditions [20][21][22][23]. Notably, despite being native RNase A not amyloidogenic [24], its oligomers can exert a suitable antitumor activity [25].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the 3D-DS mechanism is shared by some amyloidogenic proteins, such as human prion protein or cystatin C, both forming domain-swapped dimeric or oligomeric precursors of their amyloid fibrils involved in severe deposition diseases [17,18]. The toxicity of these proteins is generally ascribable to their oligomers [19,20], and these species become toxic, or not, as a function of the protein aggregation pathway(s) followed [20,21], or of the environmental pH [22,23]. However, wt-RNase A cannot undergo fibrillation, although displaying many aggregation-prone sequences [24].…”

Section: Introductionmentioning

confidence: 99%

RNase A Domain-Swapped Dimers Produced Through Different Methods: Structure–Catalytic Properties and Antitumor Activity

Montioli

Campagnari

Fasoli

et al. 2021

Life

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Upon oligomerization, RNase A can acquire important properties, such as cytotoxicity against leukemic cells. When lyophilized from 40% acetic acid solutions, the enzyme self-associates through the so-called three-dimensional domain swapping (3D-DS) mechanism involving both N- and/or C-terminals. The same species are formed if the enzyme is subjected to thermal incubation in various solvents, especially in 40% ethanol. We evaluated here if significant structural modifications might occur in RNase A N- or C-swapped dimers and/or in the residual monomer(s), as a function of the oligomerization protocol applied. We detected that the monomer activity vs. ss-RNA was partly affected by both protocols, although the protein does not suffer spectroscopic alterations. Instead, the two N-swapped dimers showed differences in the fluorescence emission spectra but almost identical enzymatic activities, while the C-swapped dimers displayed slightly different activities vs. both ss- or ds-RNA substrates together with not negligible fluorescence emission alterations within each other. Besides these results, we also discuss the reasons justifying the different relative enzymatic activities displayed by the N-dimers and C-dimers. Last, similarly with data previously registered in a mouse model, we found that both dimeric species significantly decrease human melanoma A375 cell viability, while only N-dimers reduce human melanoma MeWo cell growth.

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“…In the last years, some authors focused their attention on the application of an emerging protein, MNEI, as sweetener in beverages (Di Monaco, Miele, Picone, Masi, & Cavella, 2013;Di Monaco, Miele, Volpe, Picone, & Cavella, 2014;Picone & Temussi, 2012;Rega et al, 2015). MNEI is a variant of monellin, a natural sweet protein, and it has been demonstrated stable to acidic environments (Pica et al, 2018;Spadaccini, Leone, Rega, Richter, & Picone, 2016). Consumer demands for healthier products are leading to a large push for sugar reduction also in dairy foods (Mc Cain, Kaliappan, & Drake, 2018).…”

Section: Introductionmentioning

confidence: 99%

Temporal sweetness profile of the emerging sweetener MNEI in stirred yogurt

Miele

Leone

Cabisidan³

et al. 2019

Journal of Sensory Studies

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Yogurt is widely consumed by people under‐controlled dietary regimes. The addition of hypocaloric sweeteners to the yogurt is typically used to make them more palatable, but this may affect the fermentation phase and/or its physical and sensory characteristics. The aim of this work was to test the possible application of an emerging sweetener, MNEI, a variant of a sweet protein, monellin. In particular, its sweetness profile was compared with that of other natural sweeteners, sucrose, xylitol, and sorbitol, in yogurt. First, determinations of iso‐sweet concentration of MNEI and of those sweeteners were performed, both for set and stirred yogurts. Then, the sweetness temporal profiles of all the sweeteners were evaluated as the mean of time–intensity data (t–I). In set yogurt, the iso‐sweet concentrations of xylitol and sorbitol, but not of MNEI, were found, whereas, in stirred yogurts, the concentrations were determined for all the sweeteners. t–I results showed that sweeteners had similar behaviors, except for the end time of sweetness perception: in particular, in stirred yogurt, MNEI resulted in a more lingering sweet aftertaste. These results suggest new applications of the sweet protein MNEI in food preparations, although the combination with other natural sweeteners could be explored. Practical applications Yogurts are ideal products to develop potential applications of MNEI, a protein that has been demonstrated stable to acidic environments, and to our knowledge, this is the first report of the use of a sweet protein to sweeten viscous food preparations. Preliminary experimental results suggest new possible applications of sweet protein MNEI in food samples. In particular, it could be used to sweeten‐stirred yogurt.

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pH driven fibrillar aggregation of the super-sweet protein Y65R-MNEI: A step-by-step structural analysis

Cited by 14 publications

References 54 publications

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

RNase A Domain-Swapped Dimers Produced Through Different Methods: Structure–Catalytic Properties and Antitumor Activity

Temporal sweetness profile of the emerging sweetener MNEI in stirred yogurt

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