X‑ray Crystallographic Structure of a Compact Dodecamer from a Peptide Derived from Aβ16–36

The assembly of the
β-amyloid peptide, Aβ, into soluble
oligomers is associated with neurodegeneration in Alzheimer’s
disease. The Aβ oligomers are thought to be composed of β-hairpins.
Here, the effect of shifting the residue pairing of the β-hairpins
on the structures of the oligomers that form is explored through X-ray
crystallography. Three residue pairings were investigated using constrained
macrocyclic β-hairpins in which Aβ30–36 is juxtaposed with Aβ17–23, Aβ16–22, and Aβ15–21. The Aβ16–22–Aβ30–36 pairing
forms a compact ball-shaped dodecamer composed of fused triangular
trimers. This dodecamer may help explain the structures of the trimers
and dodecamers formed by full-length Aβ.

β-淀粉样肽（Aβ）的组装过程进入可溶性寡聚体，与阿尔茨海默病中的神经退行性病变密切相关。据推测，Aβ寡聚体由β-发夹结构组成。本研究通过X射线晶体学技术，探讨了β-发夹中残基配对的变化对形成寡聚体结构的影响。针对三种残基配对，采用受约束的大环β-发夹进行研究，其中Aβ30-36与Aβ17-23、Aβ16-22和Aβ15-21相邻。Aβ16-22-Aβ30-36的配对形成一个紧凑的球状十二聚体，由融合的三角形三聚体组成。这一十二聚体或许有助于阐释由全长Aβ形成的三聚体和十二聚体的结构。