Copper Ion Binding Site in β-Amyloid Peptide.
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 interactions 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.
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.
Diana
D
Yugay
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.
Dominic P
DP
Goronzy
Department of Chemistry and Biochemistry, University of California, Los Angeles , Los Angeles, California 90095, United States.
Lisa M
LM
Kawakami
Department of Chemistry and Biochemistry, University of California, Los Angeles , Los Angeles, California 90095, United States.
Shelley A
SA
Claridge
Department of Materials Science and Engineering, University of California, Los Angeles , Los Angeles, California 90095, United States.
Tze-Bin
TB
Song
Department of Materials Science and Engineering, University of California, Los Angeles , Los Angeles, California 90095, United States.
Zhongbo
Z
Yan
California NanoSystems Institute, University of California, Los Angeles , Los Angeles, California 90095, United States.|Department of Materials Science and Engineering, University of California, Los Angeles , Los Angeles, California 90095, United States.
Ya-Hong
YH
Xie
Department of Mathematics and Statistics, San Diego State University , San Diego, California 92182, United States.
Jérôme
J
Gilles
California NanoSystems Institute, University of California, Los Angeles , Los Angeles, California 90095, United States.|Department of Materials Science and Engineering, University of California, Los Angeles , Los Angeles, California 90095, United States.
Yang
Y
Yang
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 Materials Science and Engineering, University of California, Los Angeles , Los Angeles, California 90095, United States.
Paul S
PS
Weiss
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D010446:Peptide Fragments; D011485:Protein Binding; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D006639:Histidine; D003300:Copper
Alzheimer’s disease; binding site; histidine brace; scanning tunneling microscopy; β-amyloid; β-sheet