Monovalent cations have different effects on the assembly kinetics and morphology of α-synuclein amyloid fibrils
Journal article, 2023

Formation of α-synuclein amyloid fibrils is a pathological hallmark of Parkinson's disease and a phenomenon that is strongly modulated by environmental factors. Here, we compared effects of different monovalent cations (Li+, Na+, K+) on the formation and properties of α-synuclein amyloid fibrils. Na+ > Li+ were found to have concentration-dependent catalytic effects on primary nucleation whereas K+ ions acted inhibitory. We discuss this discrepancy in terms of a superior affinity of Na+ and Li+ to carboxylic protein groups, resulting in reduced Columbic repulsion and by considering K+ as an ion with poor protein binding and slight chaotropic character, which could promote random coil protein structure. K+ ions, furthermore, appeared to lower the β-sheet content of the fibrils and increase their persistence lengths, the latter we interpret as a consequence of lesser ion binding and hence higher line charge of the fibrils. The finding that Na+ and K+ have opposite effects on α-synuclein aggregation is intriguing in relation to the significant transient gradients of these ions across axonal membranes, but also important for the design and interpretation of biophysical assays where buffers containing these monovalent cations have been intermixedly used.

Amyloid kinetics

Sodium

salt

Potassium

Fibril morphology

α-synuclein

Author

Fritjof Havemeister

Chalmers, Life Sciences, Chemical Biology

Marziyeh Ghaeidamini

Chalmers, Life Sciences, Chemical Biology

Elin Esbjörner Winters

Chalmers, Life Sciences, Chemical Biology

Biochemical and Biophysical Research Communications

0006-291X (ISSN) 1090-2104 (eISSN)

Vol. 679 31-36

The Stability of Amyloid Fibrils - a case study on a-synuclein

Swedish Research Council (VR) (2020-05303), 2021-01-01 -- 2024-12-31.

Subject Categories

Biochemistry and Molecular Biology

Biophysics

DOI

10.1016/j.bbrc.2023.08.061

PubMed

37660641

More information

Latest update

9/12/2023