title: Copper(II)-bis-histidine coordination structure in a fibrillar amyloid β-peptide fragment and model complexes revealed by electron spin echo envelope modulation spectroscopy.
abstract: Truncated and mutated amyloid-β (Aβ) peptides are models for systematic study-in homogeneous preparations-of the molecular origins of metal ion effects on Aβ aggregation rates, types of aggregate structures formed, and cytotoxicity. The 3D geometry of bis-histidine imidazole coordination of Cu(II) in fibrils of the nonapetide acetyl-Aβ(13-21)H14A has been determined by powder (14) N electron spin echo envelope modulation (ESEEM) spectroscopy. The method of simulation of the anisotropic combination modulation is described and benchmarked for a Cu(II) -bis-cis-imidazole complex of known structure. The revealed bis-cis coordination mode, and the mutual orientation of the imidazole rings, for Cu(II) in Ac-Aβ(13-21)H14A fibrils are consistent with the proposed β-sheet structural model and pairwise peptide interaction with Cu(II) , with an alternating [-metal-vacancy-]n pattern, along the N-terminal edge. Metal coordination does not significantly distort the intra-β-strand peptide interactions, which provides a possible explanation for the acceleration of Ac-Aβ(13-21)H14A fibrillization by Cu(II) , through stabilization of the associated state and low-reorganization integration of β-strand peptide pair precursors.
authors.affiliation: Department of Physics, Emory University, Atlanta, GA 30322-2430 (USA).
authors.forename: Jessica
authors.initials: J
authors.lastname: Hernández-Guzmán
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mehta
authors.forename: Jijun
authors.initials: J
authors.lastname: Dong
authors.forename: David G
authors.initials: DG
authors.lastname: Lynn
authors.forename: Kurt
authors.initials: K
authors.lastname: Warncke
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D056831:Coordination Complexes / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006639:Histidine / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry; D008958:Models, Molecular
chemical_list: D016229:Amyloid beta-Peptides; D056831:Coordination Complexes; D007093:Imidazoles; D006639:Histidine; D003300:Copper; C029899:imidazole
keywords: EPR spectroscopy; ESEEM spectroscopy; amyloid beta-peptides; bioinorganic chemistry; copper