Dataset Information

Molecular Role of Ca2+ and Hard Divalent Metal Cations on Accelerated Fibrillation and Interfibrillar Aggregation of ?-Synuclein.

ABSTRACT: ?-Synuclein (?Syn) is an intrinsically disordered protein, the aggregation of which is highly related to the pathology of diverse ?-synucleinopathies. Various hard divalent metal cations have been shown to affect ?Syn aggregation. Especially, Ca2+ is suggested to be a crucial ion due to its physiological relevance to ?-synucleinopathies. However, the molecular origin of ?Syn aggregation mediated by the metal ions is not fully elucidated. In this study, we revealed that hard divalent metal ions had almost identical influences on ?Syn aggregation. Based on these similarities, the molecular role of Ca2+ was investigated as a representative metal ion. Herein, we demonstrated that binding of multiple Ca2+ ions induces structural transition of ?Syn monomers to extended conformations, which promotes rapid ?Syn fibrillation. Additionally, we observed that Ca2+ induced further interfibrillar aggregation via electrostatic and hydrophobic interactions. Our results from multiple biophysical methods, including ion mobility-mass spectrometry (IM-MS), synchrotron small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), provide detailed information on the structural change of ?Syn and the aggregation process mediated by Ca2+. Overall, our study would be valuable for understanding the influence of Ca2+ on the aggregation of ?Syn during the pathogenesis of ?-synucleinopathies.

SUBMITTER: Han JY

PROVIDER: S-EPMC5789889 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Publications

Molecular Role of Ca<sup>2+</sup> and Hard Divalent Metal Cations on Accelerated Fibrillation and Interfibrillar Aggregation of α-Synuclein.

Han Jong Yoon JY Choi Tae Su TS Kim Hugh I HI

Scientific reports 20180130 1

α-Synuclein (αSyn) is an intrinsically disordered protein, the aggregation of which is highly related to the pathology of diverse α-synucleinopathies. Various hard divalent metal cations have been shown to affect αSyn aggregation. Especially, Ca<sup>2+</sup> is suggested to be a crucial ion due to its physiological relevance to α-synucleinopathies. However, the molecular origin of αSyn aggregation mediated by the metal ions is not fully elucidated. In this study, we revealed that hard divalent m ...[more]

PMID: 29382893

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Project description:Among the best-studied interactions between soil phagocytic predators and a human-pathogenic fungus is that of Acanthamoeba castellanii and Cryptococcus neoformans The experimental conditions used in amoeba-fungus confrontation assays can have major effects on whether the fungus or the protozoan is ascendant in the interaction. In the presence of Mg2+ and Ca2+ in phosphate-buffered saline (PBS), C. neoformans was consistently killed when incubated with A. castellaniiA. castellanii survived better in the presence of Mg2+ and Ca2+, even when incubated with C. neoformans In the absence of Mg2+ and Ca2+, C. neoformans survived when incubated with A. castellanii, and the percentage of dead amoebae was higher than when incubated without yeast cells. These results show that the presence of Mg2+ and Ca2+ can make a decisive contribution toward tilting the outcome of the interaction in favor of the amoeba. Of the two metals, Mg2+ had a stronger effect than Ca2+ The cations enhanced A. castellanii activity against C. neoformans via enhanced phagocytosis, which is the major mechanism by which amoebae kill fungal cells. We found no evidence that amoebae use extracellular killing mechanisms in their interactions with C. neoformans In summary, the presence of Mg2+ and Ca2+ enhanced the cell adhesion on the surfaces and the motility of the amoeba, thus increasing the chance for contact with C. neoformans and the frequency of phagocytosis. Our findings imply that the divalent cation concentration in soils could be an important variable for whether amoebae can control C. neoformans in the environment.IMPORTANCE The grazing of soil organisms by phagocytic predators such as amoebae is thought to select for traits that enable some of them to acquire the capacity for virulence in animals. Consequently, knowledge about the interactions between amoebae and soil microbes, such as pathogenic fungi, is important for understanding how virulence can emerge. We show that the interaction between an amoeba and the pathogenic fungus C. neoformans is influenced by the presence in the assay of magnesium and calcium, which potentiate amoebae. The results may also have practical applications, since enriching soils with divalent cations may reduce C. neoformans numbers in contaminated soils.

Dataset Information

Molecular Role of Ca2+ and Hard Divalent Metal Cations on Accelerated Fibrillation and Interfibrillar Aggregation of ?-Synuclein.

Publications

Molecular Role of Ca<sup>2+</sup> and Hard Divalent Metal Cations on Accelerated Fibrillation and Interfibrillar Aggregation of α-Synuclein.

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