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ESEEM analysis of multi-histidine Cu(II)-coordination in model complexes, peptides, and amyloid-β.

Silva KI, Michael BC, Geib SJ, Saxena S - J Phys Chem B (2014)

Bottom Line: We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes.The ESEEM experiments carried out on systematically (15)N-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's disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.

ABSTRACT
We validate the use of ESEEM to predict the number of (14)N 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-β (Aβ). Aβ 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's 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 (15)N-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's disease etiology.

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Comparisonof ESEEM spectra of Cu(II)–PHGGGW complex andthe two-imidazole complex. Cu(II)–PHGGGW complex contains two 14N-ESEEM active nuclei.
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fig5: Comparisonof ESEEM spectra of Cu(II)–PHGGGW complex andthe two-imidazole complex. Cu(II)–PHGGGW complex contains two 14N-ESEEM active nuclei.

Mentions: Then we used the PHGGGW peptide fragment, which is the Cu(II)bindingdomain of the prion protein.17,57 Burns et al. resolvedthe Cu(II) coordination environment of the octarepeat fragment usingESR experiments and a crystal structure of the Cu(II)–PHGGGWcomplex.57 As shown in Figure 5, Cu(II) is coordinated to an imidazole nitrogenin a histidine, two backbone nitrogens from two glycine residues,and an oxygen from a carboxylic group. The structure of the Cu(II)bound HGGGW pentapeptide was found to be unstable in solution dueto the breaking of the axial water coordination.22 However, the complex still maintains the equatorial squareplanar coordination.22 Also, ESEEM resultshave indicated that histidine imidazole coordination and backbonecoordination is present in the Cu(II)–PHGGGW complex in solution.12,15 The ESEEM spectra of the Cu(II)–PHGGGW complex and the two-imidazolecomplex are shown in Figure 5 for comparison.Given the different coordination environments the two spectra do nothave identical peak positions. Importantly, the intensity of the DQpeak is different. The two-imidazole complex has a larger DQ peakcompared to the PHGGGW complex. The reported structure for the Cu(II)–PHGGGWstructure contains two 14N-ESEEM active nuclei from thedistal nitrogen of the imidazole histidine and the backbone coordinationas shown in Figure 5.15 Hence, the intensity of DQ peak is expected to be different betweenthe two complexes, as DQ peak intensity is indicative of the numberof imidazoles coordinated.47,61 However, the normalized 14N-ESEEM integrated intensity obtained for the Cu(II)–PHGGGWcomplex is similar to the integrated intensity of the two-imidazolecomplex. This information verifies that the integration method canpredict the number of 14N nuclei coupled to a Cu(II) center.


ESEEM analysis of multi-histidine Cu(II)-coordination in model complexes, peptides, and amyloid-β.

Silva KI, Michael BC, Geib SJ, Saxena S - J Phys Chem B (2014)

Comparisonof ESEEM spectra of Cu(II)–PHGGGW complex andthe two-imidazole complex. Cu(II)–PHGGGW complex contains two 14N-ESEEM active nuclei.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120975&req=5

fig5: Comparisonof ESEEM spectra of Cu(II)–PHGGGW complex andthe two-imidazole complex. Cu(II)–PHGGGW complex contains two 14N-ESEEM active nuclei.
Mentions: Then we used the PHGGGW peptide fragment, which is the Cu(II)bindingdomain of the prion protein.17,57 Burns et al. resolvedthe Cu(II) coordination environment of the octarepeat fragment usingESR experiments and a crystal structure of the Cu(II)–PHGGGWcomplex.57 As shown in Figure 5, Cu(II) is coordinated to an imidazole nitrogenin a histidine, two backbone nitrogens from two glycine residues,and an oxygen from a carboxylic group. The structure of the Cu(II)bound HGGGW pentapeptide was found to be unstable in solution dueto the breaking of the axial water coordination.22 However, the complex still maintains the equatorial squareplanar coordination.22 Also, ESEEM resultshave indicated that histidine imidazole coordination and backbonecoordination is present in the Cu(II)–PHGGGW complex in solution.12,15 The ESEEM spectra of the Cu(II)–PHGGGW complex and the two-imidazolecomplex are shown in Figure 5 for comparison.Given the different coordination environments the two spectra do nothave identical peak positions. Importantly, the intensity of the DQpeak is different. The two-imidazole complex has a larger DQ peakcompared to the PHGGGW complex. The reported structure for the Cu(II)–PHGGGWstructure contains two 14N-ESEEM active nuclei from thedistal nitrogen of the imidazole histidine and the backbone coordinationas shown in Figure 5.15 Hence, the intensity of DQ peak is expected to be different betweenthe two complexes, as DQ peak intensity is indicative of the numberof imidazoles coordinated.47,61 However, the normalized 14N-ESEEM integrated intensity obtained for the Cu(II)–PHGGGWcomplex is similar to the integrated intensity of the two-imidazolecomplex. This information verifies that the integration method canpredict the number of 14N nuclei coupled to a Cu(II) center.

Bottom Line: We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes.The ESEEM experiments carried out on systematically (15)N-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's disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.

ABSTRACT
We validate the use of ESEEM to predict the number of (14)N 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-β (Aβ). Aβ 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's 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 (15)N-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's disease etiology.

Show MeSH
Related in: MedlinePlus