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αB‐crystallin competes with Alzheimer's disease β‐amyloid peptide for peptide–peptide interactions and induces oxidation of Abeta‐Met35
Author(s) -
Narayanan Saravanakumar,
Kamps Bram,
Boelens Wilbert C.,
Reif Bernd
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.09.063
Subject(s) - peptide , crystallin , p3 peptide , amyloid (mycology) , chemistry , alzheimer's disease , biochemistry , amyloid precursor protein , disease , medicine , inorganic chemistry
We find – using solution state NMR spectroscopy – that αB‐crystallin competes efficiently for Aβ monomer–monomer interactions. Interactions between Aβ and αB‐crystallin involve the hydrophobic core residues 17–21 as well as residues 31–32 of Aβ, and thus the same chemical groups which are important for Aβ aggregation. In the presence of αB‐crystallin, Met35 in Aβ becomes efficiently oxidized. In order to quantify the redox properties of the different complexes consisting of Aβ/αB‐crystallin/copper, we suggest an NMR assay which allows to estimate the electrochemical properties indirectly by monitoring the rate of glutathion (GSH) auto‐oxidation. The oxidation of the side chain Met35 in Aβ might account for the increased neurotoxicity and the inability of Aβ to form fibrillar structures, which has been observed previously in the presence of αB‐crystallin [Stege, G.J. et al. (1999) The molecular chaperone αB‐crystallin enhances amyloid‐beta neurotoxicity. Biochem. Biophys. Res. Commun. 262, 152–156.].