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

• DOI: 10.1021/acschemneuro.0c00588
• Publication Date: 2020-12-03T16:30:44Z
• Authors: Michele F. Sciacca; Fabio Lolicato; Carmelo Tempra; Federica Scollo; Bikash R. Sahoo; Matthew D. Watson; Sara García-Viñuales; Danilo Milardi; Antonio Raudino; Jennifer C. Lee; Ayyalusamy Ramamo...; Carmelo La Rosa
• Keywords: Chaperone (clinical); Intrinsically Disordered Proteins; Co-chaperone

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