Copper(II) Coordination to Amyloid β: Murine versus Human Peptide

Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies

“…We did recently a survey of the literature about the effects of Cu(II) and Zn(II) on the aggregation of Aβ. (320,325) Several tendencies could be identified: i) Zn(II) and Cu(II) at high μM concentrations and/or in large superstoichiometric ratios compared to Aβ promote amorphous type aggregates (precipitation) over the ordered formation of fibrillar amyloids. ii) Metal ions affect the kinetics of Aβ aggregation, with the most significant impact on the nucleation phase; and iii) Cu(II) and Zn(II) affect the population and/or the type of aggregation intermediates formed.…”

“…A full dynamic and thermodynamic picture of the interactions of Aβ1-40/1-42 oligomers with metal ions or membrane is very difficult, but recent progress has been made. (31,32) …”

Structural and Computational Studies of Interactions of Metals with Amyloid Beta

“…Compared to the human peptide, the rat or mouse sequence contains the mutations R5G, H13R, and Y10F. Again using isotopically labelled EPR and NMR studies, Eury et al (2011) propose that the component II binding mode of Cu(II)/murine (1-16) is characterized by hexa-coordination, with the 3N1O equatorial binding via His 6 imidazole N, N-terminal Asp 1 NH2 and carbonyl O, and the (deprotonated) Gly 5-His 6 backbone amidyl N atom. The axial ligands proposed are the His 14 imidazole N atom and a carboxylate O atom from one of the acidic residues.…”

Cu2+-assisted two dimensional charge-mass double focusing gel electrophoresis and mass spectrometric analysis of histone variants

“…Particularly, the presence of histidine residues in peptide chains significantly enhances the metal binding abilities [35]. In any cases, the stabilities and the structures of different complexes are dependent on the location of specific amino acid residues and sequences of histone isoforms [36]. As a consequence, the chelation of histone proteins with positively charged copper(II) ions would significantly change the migration of histone isoforms in TAU gel electrophoresis, resulting in the first dimensional separation of histone isoforms based on charges.…”