Structural Properties of EGCG-Induced, Nontoxic Alzheimer's Disease Aβ Oligomers

• Published in: Journal of molecular biology 2012-08, Vol.421 (4-5), p.517-524
• Main Authors: Lopez del Amo, Juan Miguel, Fink, Uwe, Dasari, Muralidhar, Grelle, Gerlinde, Wanker, Erich E., Bieschke, Jan, Reif, Bernd
• Format: Article
• Language: English
• Subjects: Alzheimer disease; Alzheimer Disease - chemically induced; Alzheimer Disease - physiopathology; Alzheimer's disease; amyloid; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Catechin - adverse effects; Catechin - analogs & derivatives; Catechin - metabolism; drug development; drugs; green tea; Humans; hydrophobicity; magic angle spinning (MAS) solid-state NMR spectroscopy; Magnetic Resonance Spectroscopy; Neuroprotective Agents - adverse effects; Neuroprotective Agents - metabolism; neurotoxicity; nuclear magnetic resonance spectroscopy; Protein Conformation; Protein Denaturation; Protein Multimerization; β-amyloid peptide
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2012.01.013

The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease β-amyloid peptide (Aβ) neurotoxicity. Solution-state NMR allows probing initial EGCG–Aβ interactions. We show that EGCG-induced Aβ oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of Aβ. The C-terminal part of the Aβ peptide (residues 22–39) adopts a β-sheet conformation, whereas the N-terminus (residues 1–20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Aβ aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development. [Display omitted] ► EGCG-induced Aβ oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. ► EGCG interferes with the aromatic hydrophobic core of Aβ. ► The C-terminal part of the Aβ peptide (residues 22–39) adopts a β-sheet conformation, whereas the N-terminus (residues 1–20) is unstructured. ► The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Aβ aggregates as well.