title: Molecular Simulations of Human and Mouse Aβ1-16 at Different pH Values: Structural Characteristics toward Understanding Cu(2+) -Coordinated Amyloid Beta Spheres.
abstract: As the main sequence responsible for metal ion coordination in the amyloid beta (Aβ) peptide, Aβ1-16 plays a key role in the understanding of the aggregation of Aβ induced by Cu(2+) ions. There is no consensus on the nature of the coordination sphere of the Cu(2+) -Aβ complex so far due to the amorphous conformation of the Aβ1-16 peptide itself and the pH dependence of Cu(2+) -Aβ coordination. The simulation reported here reveals that human Aβ1-16 monomer has a U-shape morphology, which is preserved at any pH. This morphology accommodates Cu(2+) ions with several binding sites and is also the basis for establishing a center-distance statistical method (CDSM). Based on this CDSM, specific histidine residues for a Cu(2+) -coordinated sphere are identified and the corresponding accurate pH range is established, indicating that the CDSM can be used as a reference to predict the potential coordination sites of metal ions in other amorphous peptides. By contrast, mouse Aβ1-16 monomer has a more open and random morphology than human Aβ1-16 due to the differences of three sequence positions. These mutations not only reduce the number of binding sites required by a stable Cu(2+) -binding sphere but also diminish the capacity to generate salt bridges compared to the human peptide. These observations offer insights into the roles of three residues that differ in the mouse Aβ1-16 and perhaps into the reasons mice seldom develop Alzheimer's disease.
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China. chm_aihq@ujn.edu.cn.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Ai
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhu
authors.affiliation: School of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D003300:Copper / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C433241:amyloid beta-protein (1-16); D003300:Copper
keywords: Alzheimer′s disease; amyloid beta peptides; center-distance statistical method; coordination spheres; mouse/human peptides