Amphiphilic Adsorption of Human Islet Amyloid Polypeptide Aggregates to Lipid/Aqueous Interfaces

JOURNAL OF MOLECULAR BIOLOGY

卷:421

Article

Xiao, Dequan¹  Fu, Li¹  Liu, Jian¹  Batista, Victor S.¹  Yan, Elsa C. Y.¹ 

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

关键词: sum frequency generation spectroscopy;    vibrational hyperpolarizability;    human islet amyloid polypeptide;    divide-and-conquer normal mode analysis;    ab initio simulation of SFG spectra;   

DOI  :  10.1016/j.jmb.2011.12.035

来源: Elsevier

【 摘 要 】

Many amyloid proteins misfold into beta-sheet aggregates upon interacting with biomembranes at the onset of diseases, such as Parkinson's disease and type H diabetes. The molecular mechanisms triggering aggregation depend on the orientation of beta-sheets at the cell membranes. However, understanding how beta-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 beta-strands oriented at 48 degrees relative to the interface. This orientation reflects the amphiphilic properties of hIAPP beta-sheet aggregates and suggests the potential disruptive effect on membrane integrity. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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