Influence of <scp>pH</scp> on the structure and stability of the sweet protein MNEI

Spadaccini, Roberta; Leone, Serena; Rega, Michele F.; Richter, Christian; Picone, Delia

doi:10.1002/1873-3468.12437

Cited by 20 publications

(8 citation statements)

References 33 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…HFIP exerts its described helix-stabilizing effect when present up to 60%, but further decreasing the medium polarity has detrimental effects on the peptide structure. In fact, the decrease of the dielectric constant can have a dramatic influence on the pK a of amino acid side-chains (Spadaccini et al, 2016 ), due to the stabilization of uncharged states, which, in this case, would reduce the positive influence of both helix capping effects.…”

Section: Resultsmentioning

confidence: 99%

Disordered Peptides Looking for Their Native Environment: Structural Basis of CB1 Endocannabinoid Receptor Binding to Pepcans

Emendato

Guerrini

Marzola

et al. 2018

Front. Mol. Biosci.

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Endocannabinoid peptides, or “pepcans,” are endogenous ligands of the CB1 cannabinoid receptor. Depending on their length, they display diverse activity: For instance, the nona-peptide Pepcan-9, also known as hemopressin, is a powerful inhibitor of CB1, whereas the longer variant Pepcan-12, which extends by only three amino acid residues at the N-terminus, acts on both CB1 and CB2 as an allosteric modulator, although with diverse effects. Despite active research on their pharmacological applications, very little is known about structure-activity relationships of pepcans. Different structures have been proposed for the nona-peptide, which has also been reported to form fibrillar aggregates. This might have affected the outcome and reproducibility of bioactivity studies. In an attempt of elucidating the determinants of both biological activity and aggregation propensity of Pepcan-9 and Pepcan-12, we have performed their structure characterization in solvent systems characterized by different polarity and pH. We have found that, while disordered in aqueous environment, both peptides display helical structure in less polar environment, mimicking the proteic receptor milieu. In the case of Pepcan-9, this structure is fully consistent with the observed modulation of the CB1. For Pepcan-12, whose allosteric binding site is still unknown, the presented structure is compatible with the binding at one of the previously proposed allosteric sites on CB1. These findings open the way to structure-driven design of selective peptide modulators of CB1.

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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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Influence of pH on the structure and stability of the sweet protein MNEI

Cited by 20 publications

References 33 publications

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

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

Disordered Peptides Looking for Their Native Environment: Structural Basis of CB1 Endocannabinoid Receptor Binding to Pepcans

Temporal sweetness profile of the emerging sweetener MNEI in stirred yogurt

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