Polymorphism of Oligomers of a Peptide from 尾-Amyloid

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• 作者：Johnny D. Pham ; Borries Demeler ; James S. Nowick
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：April 9, 2014
• 年：2014
• 卷：136
• 期：14
• 页码：5432-5442
• 全文大小：882K
• 年卷期：v.136,no.14(April 9, 2014)
• ISSN：1520-5126

文摘

This contribution reports solution-phase structural studies of oligomers of a family of peptides derived from the 尾-amyloid peptide (A尾). We had previously reported the X-ray crystallographic structures of the oligomers and oligomer assemblies formed in the solid state by a macrocyclic 尾-sheet peptide containing the A尾_15鈥?3 nonapeptide. In the current study, we set out to determine its assembly in aqueous solution. In the solid state, macrocyclic 尾-sheet peptide 1 assembles to form hydrogen-bonded dimers that further assemble in a sandwich-like fashion to form tetramers through hydrophobic interactions between the faces bearing V₁₈ and F₂₀. In aqueous solution, macrocyclic 尾-sheet peptide 1 and homologue 2a form hydrogen-bonded dimers that assemble to form tetramers through hydrophobic interactions between the faces bearing L₁₇, F₁₉, and A₂₁. In the solid state, the hydrogen-bonded dimers are antiparallel, and the 尾-strands are fully aligned, with residues 17鈥?3 of one of the macrocycles aligned with residues 23鈥?7 of the other. In solution, residues 17鈥?3 of the hydrogen-bonded dimers are shifted out of alignment by two residues toward the C-termini. The two hydrogen-bonded dimers are nearly orthogonal in the solid state, while in solution the dimers are only slightly rotated. The differing morphology of the solution-state and solid-state tetramers is significant, because it may provide a glimpse into some of the structural bases for polymorphism among A尾 oligomers in Alzheimer鈥檚 disease.