Amphiphilic adsorption of human islet amyloid polypeptide aggregates to lipid/aqueous interfaces |
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Authors: | Xiao Dequan Fu Li Liu Jian Batista Victor S Yan Elsa C Y |
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Institution: | Department of Chemistry, Yale University, New Haven, CT 06520, USA. |
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Abstract: | Many amyloid proteins misfold into β-sheet aggregates upon interacting with biomembranes at the onset of diseases, such as Parkinson's disease and type II diabetes. The molecular mechanisms triggering aggregation depend on the orientation of β-sheets at the cell membranes. However, understanding how β-sheets adsorb onto lipid/aqueous interfaces is challenging. Here, we combine chiral sum frequency generation (SFG) spectroscopy and ab initio quantum chemistry calculations based on a divide-and-conquer strategy to characterize the orientation of human islet amyloid polypeptides (hIAPPs) at lipid/aqueous interfaces. We show that the aggregates bind with β-strands oriented at 48° relative to the interface. This orientation reflects the amphiphilic properties of hIAPP β-sheet aggregates and suggests the potential disruptive effect on membrane integrity. |
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