Kinetics of the Interactions between Copper and Amyloid‐β with FAD Mutations and Phosphorylation at the N terminus
| Autor: | Paul Girvan, Toru Miyake, Thomas Branch, Liming Ying, Xiangyu Teng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Reaction mechanism Kinetics chemistry.chemical_element Peptide Biochemistry Dissociation (chemistry) 03 medical and health sciences Alzheimer Disease Humans Phosphorylation Molecular Biology Ternary complex chemistry.chemical_classification Amyloid beta-Peptides Full Paper Organic Chemistry 0601 Biochemistry And Cell Biology Full Papers fluorescence spectroscopy Copper 0304 Medicinal And Biomolecular Chemistry N-terminus 030104 developmental biology chemistry copper Mutation Molecular Medicine reaction mechanism |
| Zdroj: | Chembiochem |
| ISSN: | 1439-7633 1439-4227 |
| Popis: | Mutations and post‐translational modifications of amyloid‐β (Aβ) peptide in its N terminus have been shown to increase fibril formation, yet the molecular mechanism is not clear. Here we investigated the kinetics of the interactions of copper with two Aβ peptides containing Familial Alzheimer's disease (FAD) mutations (English (H6R) and Tottori (D7N)), as well as with Aβ peptide phosphorylated at serine 8 (pS8). All three peptides bind to copper with a similar rate as the wild‐type (wt). The dissociation rates follow the order pS8>H6R>wt>D7N; the interconversion between the two coordinating species occurs 50 % faster for H6R and pS8, whereas D7N had only a negligible effect. Interestingly, the rate of ternary complex (copper‐bridged heterodimer) formation for the modified peptides was significantly faster than that for wt, thus leading us to propose that FAD and sporadic AD might share a kinetic origin for the enhanced oligomerisation of Aβ. |
| Databáze: | OpenAIRE |
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