Copper(II)-bis-histidine coordination structure in a fibrillar amyloid ?-peptide fragment and model complexes revealed by electron spin echo envelope modulation spectroscopy.

ABSTRACT: Truncated and mutated amyloid-? (A?) peptides are models for systematic study-in homogeneous preparations-of the molecular origins of metal ion effects on A? 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-A?(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-A?(13-21)H14A fibrils are consistent with the proposed ?-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-?-strand peptide interactions, which provides a possible explanation for the acceleration of Ac-A?(13-21)H14A fibrillization by Cu(II) , through stabilization of the associated state and low-reorganization integration of ?-strand peptide pair precursors.

SUBMITTER: Hernandez-Guzman J 

PROVIDER: S-EPMC3864031 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature