Copper(II)-bis-Histidine Coordination Structure in a Fibrillar Amyloid β-Peptide Fragment and Model Complexes Revealed by Electron Spin Echo Envelope Modulation Spectroscopy
Copper(II)-bis-Histidine Coordination Structure in a Fibrillar Amyloid β-Peptide Fragment and Model Complexes Revealed by Electron Spin Echo Envelope Modulation Spectroscopy
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DOI：
10.1002/cbic.201300236
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发表时间：
2013-09-23
期刊：
影响因子：
3.2
通讯作者：
Warncke, Kurt
中科院分区：
文献类型：
--
作者：
Hernandez-Guzman, Jessica;Sun, Li;Warncke, Kurt
截短和突变的淀粉样蛋白-β（A β）肽是用于系统研究的模型-在均匀的澄清-金属离子对A β聚集率的影响的分子起源，形成的聚集体结构的类型，和细胞毒性。用粉末N-14电子自旋回波包络调制（ESEEM）光谱法测定了乙酰基-A β（13-21）H14 A原纤维中Cu-Ⅱ的双组氨酸咪唑配位的三维几何构型。模拟的各向异性组合调制的方法描述和基准为铜-II-双-顺-咪唑配合物的已知结构。Ac-A β（13-21）H14 A原纤维中Cu-II的双-顺式配位模式和咪唑环的相互取向与提出的β-折叠结构模型和与Cu-II的成对肽相互作用一致，沿着N-末端边缘具有交替的[-金属-空位-]（n）模式。金属配位不会显著扭曲β链内肽相互作用，这为Cu-II通过稳定β链肽对前体的缔合状态和低重组整合加速Ac-A β（13-21）H14 A的絮凝提供了可能的解释。
Truncated and mutated amyloid-beta (A beta) peptides are models for systematic study-in homogeneous preparations-of the molecular origins of metal ion effects on A beta 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 beta(13-21)H14A has been determined by powder N-14 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 beta(13-21)H14A fibrils are consistent with the proposed beta-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-beta-strand peptide interactions, which provides a possible explanation for the acceleration of Ac-A beta(13-21)H14A fibrillization by Cu-II, through stabilization of the associated state and low-reorganization integration of beta-strand peptide pair precursors.