Amphiphilic adsorption of human islet amyloid polypeptide aggregates to lipid/aqueous interfaces.
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.
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Dequan
D
Xiao
Li
L
Fu
Jian
J
Liu
Victor S
VS
Batista
Elsa C Y
EC
Yan
D000327:Adsorption; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D055503:Protein Multimerization; D013057:Spectrum Analysis; D014867:Water / Q000378:metabolism*
D058228:Islet Amyloid Polypeptide; D008055:Lipids; D014867:Water