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摘要
As the main sequence responsible for metal ion coordination in the amyloid beta (A beta) peptide, A beta(1-16) plays a key role in the understanding of the aggregation of Ab induced by Cu2+ ions. There is no consensus on the nature of the coordination sphere of the Cu2+-A beta complex so far due to the amorphous conformation of the A beta(1-16) peptide itself and the pH dependence of Cu2+-A beta coordination. The simulation reported here reveals that human AA beta(1-16) monomer has a U-shape morphology, which is preserved at any pH. This morphology accommodates Cu2+ 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 Cu2+-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 A beta(1-16) monomer has a more open and random morphology than human A beta(1-16) due to the differences of three sequence positions. These mutations not only reduce the number of binding sites required by a stable Cu2+-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 A beta(1-16) and perhaps into the reasons mice seldom develop Alzheimer's disease.
- 出版日期2016-6-3
- 单位济南大学
