Divalent copper ion bound amyloid-beta(40) and amyloid-beta(42) alloforms are less preferred than divalent zinc ion bound amyloid-beta(40) and amyloid-beta(42) alloforms

作者：Coskuner Orkid^*

来源：Journal of Biological Inorganic Chemistry, 2016, 21(8): 957-973.

DOI：10.1007/s00775-016-1392-5

• Disordered proteins
• Metalloproteins
• Copper
• Zinc
• Amyloid-beta
• Molecular dynamics

Divalent copper and zinc ions bind to the amyloid-beta(40) and amyloid-beta(42) alloforms and affect their structural stability as well as their chemical and physical properties. Current literature debates the impact of copper ions on amyloid-beta alloforms. Recently, we reported the structural and thermodynamic properties of apo amyloid-beta and divalent zinc ion bound amyloid-beta alloforms (see, Wise-Scira et al. in J Biol Inorg Chem 17:927-938, 2012 and Coskuner et al. in ACS Chem Neurosci 4: 310-320, 2013). In our search for understanding the impacts of transition metal ions on disordered amyloid-beta, we also developed and reported new potential functions using quantum mechanics, which are required for high-quality molecular dynamics simulations of divalent copper ion bound amyloid-beta alloforms (see, Wise and Coskuner in J Comput Chem 35:1278-1289, 2014). The structures and thermodynamic properties of the divalent copper ion bound amyloid-beta(40) and amyloid-beta(42) alloforms in an aqueous medium are studied. The secondary and tertiary structures of divalent copper ion bound amyloid-beta(40) and amyloid-beta(42) along with their thermodynamic properties including enthalpy, entropy, Gibbs free energy and potential of mean force surface are investigated. Results are compared to those for apo amyloid-beta and divalent zinc ion bound amyloid-beta alloforms. Results demonstrate that copper binding to A beta alloforms is thermodynamically less preferred rather than zinc binding. Less compact structures of copper ion bound amyloid-beta alloforms possess reduced stability in comparison to zinc ion bound amyloid-beta alloforms. Cu(II) binding impacts the thermodynamic properties, secondary and tertiary structural properties of A beta 40 and A beta 42.

• 出版日期2016-12