Figure 3. Scanning tunneling microscopy images of Aβ1−16-Cu2+ (a,b) and Aβ1−16 (c,d). Imaging conditions: (a,b) 10 nm × 10 nm, Vsample = 0.55 V, Itunnel =10pA;(c)10nm×10nm,Vsample =0.25V,Itunnel =17pA;(d)10nm×10nm,Vsample =0.30V,Itunnel =14pA.
β-Amyloid aggregates in the brain play critical roles in Alzheimer’s disease, a chronic neurodegenerative condition. Amyloid-associated metal ions, particularly zinc and copper ions, have been implicated in disease pathogenesis. Despite the importance of such ions, the binding sites on the β-amyloid peptide remain poorly understood. In this study, we use scanning tunneling microscopy, circular dichroism, and surface-enhanced Raman spectroscopy to probe the inter-actions between Cu2+ ions and a key β-amyloid peptide fragment, consisting of the first 16 amino acids, and define the copper−peptide binding site. We observe that in the presence of Cu2+, this peptide fragment forms β-sheets, not seen without the metal ion. By imaging with scanning tunneling microscopy, we are able to identify the binding site, which involves two histidine residues, His13 and His14. We conclude that the binding of copper to these residues creates an interstrand histidine brace, which enables the formation of β-sheets.
Nano Letters 2016, 16, 6282-6289
Diana Yugay,†,‡ Dominic P. Goronzy,†,‡ Lisa M. Kawakami,‡ Shelley A. Claridge,‡,§,∥ Tze-Bin Song,⊥ ZhongboYan,⊥ Ya-HongXie,*,†,⊥ Jeŕom̂eGilles,*,∇ YangYang,*,†,⊥ and PaulS.Weiss*,†,‡,⊥
†California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States
‡Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States
§Department of Chemistry and ∥Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States
⊥Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
∇Department of Mathematics and Statistics, San Diego State University, San Diego, California 92182, United States
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