Localization of the noncovalent binding site between amyloid-beta-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry.
Abnormal accumulation and aggregation of amyloid-beta-peptide (Abeta) eventually lead to the formation and cerebral deposition of amyloid plaques, the major pathological hallmark in Alzheimer's disease (AD). Oleuropein (OE), an Olea europaea L. derived polyphenol, exhibits a broad range of pharmacological properties, such as antioxidant, anti-inflammatory, and antiatherogenic, which could serve as combative mechanisms against several reported pathways involved in the pathophysiology of AD. The reported noncovalent interaction between Abeta and OE could imply a potential antiamyloidogenic role of the latter on the former via stabilization of its structure and prevention of the adaptation of a toxic beta-sheet conformation. The established beta-sheet conformation of the Abeta hydrophobic carboxy-terminal region and the dependence of its toxicity and aggregational propensity on its secondary structure make the determination of the binding site between Abeta and OE highly important for assessing the role of the interaction. In this study, two different proteolytic digestion protocols, in conjunction with high-sensitivity electrospray ionization mass spectrometric analysis of the resulting peptide fragments, were used to determine the noncovalent binding site of OE on Abeta and revealed the critical regions for the interaction.
Bazoti
Fotini N
FN
GAIA Research Center, Bioanalytical Laboratory, The Goulandris Natural History Museum, Kifissia, Greece.
Bergquist
Jonas
J
Markides
Karin
K
Tsarbopoulos
Anthony
A
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D017357:Cyclotrons; D005583:Fourier Analysis; D006801:Humans; D006868:Hydrolysis; D057888:Iridoid Glucosides; D039823:Iridoids; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011714:Pyrans / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D014357:Trypsin / Q000737:chemistry
D016229:Amyloid beta-Peptides; D057888:Iridoid Glucosides; D039823:Iridoids; D010446:Peptide Fragments; D011714:Pyrans; C002769:oleuropein; D014357:Trypsin