Details

Autor(en) / Beteiligte

• Uceda, Ana Belén
• Ramis, Rafael
• Pauwels, Kris
• Adrover, Miquel
• Mariño, Laura
• Frau, Juan
• Vilanova, Bartolomé

Titel

Understanding the effect of the membrane-mimetic micelles on the interplay between α-synuclein and Cu(II)/Cu(I) cations

Ist Teil von

• Journal of inorganic biochemistry, 2023-10, Vol.247, p.112344-112344, Article 112344

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• α-Synuclein (αS) is a presynaptic protein whose aggregates are considered as a hallmark of Parkinson's disease (PD). Although its physiological function is still under debate, it is widely accepted that its functions are always mediated by its interaction with membranes. The association of αS with phospholipid membranes occurs concomitant to its folding from its monomeric, unfolded state towards an antiparallel amphipathic α-helix. Besides this, copper ions can also bind αS and modify its aggregation propensity. The effect of Cu(II) and Cu(I) on the lipid-αS affinity and on the structure of the membrane-bound αS have not yet been studied. This knowledge is relevant to understand the molecular pathogenesis of PD. Therefore, we have here studied the affinities between Cu(II) and Cu(I) and the micelle-bound αS, as well as the effect of these cations on the structure of micelle-bound αS. Cu(II) or Cu(I) did not affect the α-helical structure of the micelle-bound αS. However, while Cu(I) binds at the same sites of αS in the presence or in the absence of micelles, the micelle-bound αS displays different Cu(II) binding sites than unbound αS. In any case, sodium docecyl sulphate -micelles reduce the stability of the αS complexes with both Cu(II) and Cu(I). Finally, we have observed that the micelle-bound αS is still able to prevent the Cu(II)-catalysed oxidation of neuronal metabolites (e.g. ascorbic acid) and the formation of reactive oxygen species, thus this binding does not impair its biological function as part of the antioxidant machinery. The affinities between Cu(II)/Cu(I) and the micelle-bound α-synuclein were studied, as well as the effect of these cations on the structure of the protein. Micelles reduce the stability of the protein complexes with both Cu(II) and Cu(I); however, micelle-bound α-synuclein is still able to prevent the Cu(II)-catalysed oxidation of neuronal metabolites. [Display omitted] •Cu(II) or Cu(I) did not affect the α-helical structure of micelle-bound α-synuclein.•The micelle-bound α-synuclein displays different Cu(II) binding sites than unbound protein.•Micelles reduce the stability of the α-synuclein complexes with both Cu(II) and Cu(I).•Micelles-bound α-synuclein prevents the Cu(II) catalysed oxidation of neuronal metabolites