The density of anionic lipids modulates the adsorption of α-Synuclein onto lipid membranes

Andersson, Alexandra; Linse, Sara; Sparr, Emma; Fornasier, Marco; Jönsson, Peter

doi:10.1016/j.bpc.2023.107143

Cited by 5 publications

(2 citation statements)

References 47 publications

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“…α-Synuclein adsorption increases with increasing fraction of charged lipids up to a certain fraction, whereas for higher content of anionic lipids it reaches saturation and appears insensitive to variations in membrane charge density. 40 The electrostatic attraction between negatively charged lipid headgroups and positively charged amino acids flanking the hydrophobic and hydrophilic faces of the α-helix likely stabilizes the membrane-bound state ( Figure 1 D). In addition, the electrostatic repulsion between the positively charged helices of adjacent adsorbed protein molecules may be screened at a negatively charged membrane.…”

Section: Driving Forces For α-Synuclein Adsorption To Lipid Membranesmentioning

confidence: 99%

“…This is consistent with experimental observations. 40 , 42 It has been shown that α-synuclein associates with membranes in fluid state, while much less association has been observed for gel phase membranes with solid hydrocarbon chains. 42 The fluid and the gel state membranes are clearly different with respect to both the hydrophobicity of the membrane interface (see Driving Forces for α-Synuclein Adsorption to Lipid Membranes ) and the lipid dynamics, in particular the lateral diffusion of the lipids in the membrane.…”

Section: Membrane Fluidity and Curvature Effectsmentioning

confidence: 99%

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Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation

Makasewicz,

Linse,

Sparr

2024

JACS Au

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α-Synuclein is a small neuronal protein enriched at presynaptic termini. It is hypothesized to play a role in neurotransmitter release and synaptic vesicle cycling, while the formation of α-synuclein amyloid fibrils is associated with several neurodegenerative diseases, most notably Parkinson’s Disease. The molecular mechanisms of both the physiological and pathological functions of α-synuclein remain to be fully understood, but in both cases, interactions with membranes play an important role. In this Perspective, we discuss several aspects of α-synuclein interactions with lipid membranes including cooperative adsorption, membrane remodeling and α-synuclein amyloid fibril formation in the presence of lipid membranes. We highlight the coupling between the different phenomena and their interplay in the context of physiological and pathological functions of α-synuclein.

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Section: Driving Forces For α-Synuclein Adsorption To Lipid Membranesmentioning

confidence: 99%

Section: Membrane Fluidity and Curvature Effectsmentioning

confidence: 99%

Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation

Makasewicz,

Linse,

Sparr

2024

JACS Au

Self Cite

View full text Add to dashboard Cite

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Thermodynamics of oligomerization and Helix-to-sheet structural transition of amyloid β-protein on anionic phospholipid vesicles

Ikeda,

Sugiura,

Nakao

et al. 2024

Biophysical Chemistry

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Accelerated Amyloid Aggregation Dynamics of Intrinsically Disordered Proteins in Heavy Water

Son,

Im,

Hyun

et al. 2024

J. Phys. Chem. Lett.

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We explored the influence of D 2 O on the fibrillation kinetics and structural dynamics of amyloid intrinsically disordered proteins (IDPs), including α-synuclein, amyloid-β 1−42, and K18. Our findings revealed that fibrillation of IDPs was accelerated in D 2 O compared to that in H 2 O, exhibiting faster kinetics in contrast to the structured protein, insulin. Structural investigations using electrospray ionization ion mobility mass spectrometry and small-angle Xray scattering combined with molecular dynamics simulations demonstrated that IDPs did not show significant structural changes that could influence accelerated fibrillation in D 2 O. Umbrella sampling of protein protofibrils verified that an increased level of hydrogen bonding of D 2 O and enhanced hydrophobic interactions stabilized β-sheet structured fibrils in D 2 O. These findings indicate that stabilizing β-sheet fibrils and a more hydrophobic microenvironment in D 2 O result in enhanced and faster fibrillation of IDPs. The study highlights the importance of considering D 2 O's differential impact on protein interactions when conducting structural and kinetic analyses, particularly for native peptides and proteins.

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The density of anionic lipids modulates the adsorption of α-Synuclein onto lipid membranes

Cited by 5 publications

References 47 publications

Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation

Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation

Thermodynamics of oligomerization and Helix-to-sheet structural transition of amyloid β-protein on anionic phospholipid vesicles

Accelerated Amyloid Aggregation Dynamics of Intrinsically Disordered Proteins in Heavy Water

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