Identification of the molecular interaction site of amyloid beta peptide by using a fluorescence assay.
Beta-amyloid peptides (Abeta) are the main protein components of neuritic plaques and are important in the pathogenesis of Alzheimer's disease. It is reported that Abeta itself is not toxic; however, it becomes toxic to neuronal cells once it has aggregated into amyloid fibrils by peptide-peptide interactions. In this study, to specify the molecular mechanism of aggregation, a novel fluorescence assay was designed. For this purpose, possible partial peptides (38 types of 5-mer) were synthesized on solid-phase. The molecular interactions were examined by a fluorescence probe possessing Lys-Leu-Val-Phe-Phe (KLVFF) as a molecular recognition site. KLVFF is known to be a minimum sequence for formation of the Abeta aggregate. A specific interaction was observed between labeled and immobilized KLVFF. It suggests that the aggregation of Abeta was controlled by the recognition of KLVFF itself by hydrophobic and electrostatic interactions.
Watanabe
K
K
National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Segawa
T
T
Nakamura
K
K
Kodaka
M
M
Konakahara
T
T
Okuno
H
H
D000544:Alzheimer Disease / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000302:isolation & purification* / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D009842:Oligopeptides; D010446:Peptide Fragments