pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-尾 peptide

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• 作者：Leila Ghalebani¹ ; ^{leila.ghalebani@ki.se} ; Anna Wahlströ ; m ^{anna.wahlstrom@dbb.su.se} ; Jens Danielsson ^{jensd@dbb.su.se} ; Sebastian K.T.S. Wä ; rmlä ; nder ^{seb@dbb.su.se} ; Astrid Grä ; slund ; ^{astrid@dbb.su.se}
• 关键词：Alzheimer&rsquo ; s disease ; Amyloid-尾 peptide ; NMR spectroscopy ; Copper and zinc ; Metal ions ; Metal binding
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：11 May, 2012
• 卷：421
• 期：3
• 页码：554-560
• 文件大小：885 K

摘要

Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer鈥檚 disease amyloid plaques. The amyloid-尾 (A尾) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with ¹⁵N- and ¹³C,¹⁵N-labeled A尾(1-40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to A尾 may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the A尾 peptide under these conditions.