Authors: Luc Guilloreau Luminita Damian Yannick Coppel Honoré Mazarguil Mathias Winterhalter Peter Faller
Publish Date: 2006/08/22
Volume: 11, Issue: 8, Pages: 1024-1038
Abstract
The aggregation of the peptide amyloidβ Aβ to form amyloid plaques is a key event in Alzheimer’s disease It has been shown that CuII can bind to soluble Aβ and influence its aggregation properties Three histidines and the Nterminal amine have been proposed to be involved in its coordination Here for the first time we show isothermal titration calorimetry ITC measurements of the CuII binding to Aβ16 and Aβ28 models of the soluble Aβ Moreover different spectroscopic methods were applied The studies revealed new insights into these CuII–Aβ complexes 1 ITC showed two CuII binding sites with an apparent K d of 10−7 and 10−5 M respectively 2 the highaffinity site has a smaller enthalpic contribution but a larger entropic contribution than the lowaffinity binding site 3 azide did not bind to CuII in the higheraffinity binding site suggesting the absence of a weak labile ligand 4 azide could bind to the CuII in the lowaffinity binding site in Aβ28 but not in Aβ16 5 1HNMR suggests that the carboxylate of aspartic acid in position 1 is involved in the ligation to CuII in the highaffinity binding site 6 the pK a of 113 of tyrosine in position 10 was not influenced by the binding of 2 equivalents of CuII
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