ESEEM Analysis of Multi-Histidine Cu(II)-Coordination in Model Complexes, Peptides, and Amyloid-尾

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• 作者：K. Ishara Silva ; Brian C. Michael ; Steven J. Geib ; Sunil Saxena
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：July 31, 2014
• 年：2014
• 卷：118
• 期：30
• 页码：8935-8944
• 全文大小：472K
• ISSN：1520-5207

文摘

We validate the use of ESEEM to predict the number of ¹⁴N nuclei coupled to a Cu(II) ion by the use of model complexes and two small peptides with well-known Cu(II) coordination. We apply this method to gain new insight into less explored aspects of Cu(II) coordination in amyloid-尾 (A尾). A尾 has two coordination modes of Cu(II) at physiological pH. A controversy has existed regarding the number of histidine residues coordinated to the Cu(II) ion in component II, which is dominant at high pH (8.7) values. Importantly, with an excess amount of Zn(II) ions, as is the case in brain tissues affected by Alzheimer鈥檚 disease, component II becomes the dominant coordination mode, as Zn(II) selectively substitutes component I bound to Cu(II). We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes. The ESEEM experiments carried out on systematically ¹⁵N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6. Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer鈥檚 disease etiology.