Probing Molecular Interactions in Metal-Abeta Complexes and Supramolecular Coiled Coil Assemblies Using Electron Spin Resonance

摘要: In this work we focus on details of Cu(II) coordination in amyloid-β (Aβ) peptide. Aggregation Aβ, and modulation morphology aggregates by divalent metal ions, such as Zn(II), are important the etiology Alzheimer’s disease. The ion amyloidogenic proteins heterogeneous involves one or more histidine residues. Aβ peptide contains three residues at positions 6, 13, 14. number coordinated to depends environmental factors pH, concentration, presence other metals, ionic strength etc. With aid electron spin resonance (ESR) show that physiological Zn(II) ions selectively substitute disrupt distribution population among different modes. We also quantify higher pH 8.7. Our results suggests simultaneous His13-His14 may lead formation with amorphous morphology. Furthermore importance His13 ordered β-sheets. Overall rationalize impact modulating aggregates. second part our research examine molecular origins flexibility associated supramolecular polymer subunits double (DEER) spectroscopy. It has been shown coiled coil appended organic linkers, ethylenediamide (EDA) piperazine (PIP), led assemblies apparent hydrodynamic radii. strategic placement label near cross linking site N-terminus were able monitor range conformations each subunit when linked two linkers. Molecular dynamics simulations guided DEER distance distributions conducted PIP linker stabilizes a folded where positioning outer helices is constrained. suggest subpopulation facilitate chain propagation same direction leading polymers larger radius.