Lipid-Chaperone Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins

0536884 - ÚOCHB 2021 RIV US eng J - Journal Article
Sciacca, M. F. - Lolicato, F. - Tempra, Carmelo - Scollo, Federica - Sahoo, B. R. - Watson, M. D. - García-Viñuales, S. - Milardi, D. - Raudino, A. - Lee, J. - Ramamoorthy, A. - La Rosa, C.
Lipid-Chaperone Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins.
ACS Chemical Neuroscience. Roč. 11, č. 24 (2020), s. 4336-4350. ISSN 1948-7193. E-ISSN 1948-7193
R&D Projects: GA ČR(CZ) GX19-26854X
Institutional support: RVO:61388963 ; RVO:61388955
Keywords : intrinsically disordered proteins * lipid-chaperone hypothesis * Alzheimer * Parkinson * diabetes mellitus * oxidized lipids
OECD category: Physical chemistry; Physical chemistry (UFCH-W)
Impact factor: 4.418, year: 2020
Method of publishing: Limited access
https://doi.org/10.1021/acschemneuro.0c00588

An increasing number of human diseases has been shown to be linked to aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, and α-synuclein are, indeed, involved in type-II diabetes, Alzheimer’s, and Parkinson’s, respectively. Despite the correlation of the toxicity of these proteins at early aggregation stages with membrane damage, the molecular events underlying the process is quite complex to understand. In this study, we demonstrate the crucial role of free lipids in the formation of lipid–protein complex, which enables an easy membrane insertion for amylin, amyloid-β, and α-synuclein. Experimental results from a variety of biophysical methods and molecular dynamics results reveal that this common molecular pathway in membrane poration is shared by amyloidogenic (amylin, amyloid-β, and α-synuclein) and nonamyloidogenic (rat IAPP, β-synuclein) proteins. Based on these results, we propose a “lipid-chaperone” hypothesis as a unifying framework for protein–membrane poration.
Permanent Link: http://hdl.handle.net/11104/0314634


Research data: Zenodo