ACS Chem Neurosci. 2020 Aug 5;11(15):2340-2347. doi: 10.1021/acschemneuro.0c00290. Epub 2020 Jul 14.
High-resolution structures of oligomers formed by the β-amyloid peptide, Aβ, are important for understanding the molecular basis of Alzheimer's disease. Dimers of Aβ are linked to the pathogenesis and progression of Alzheimer's disease, and tetramers of Aβ are neurotoxic. This paper reports the X-ray crystallographic structures of dimers and tetramers, as well as an octamer, formed by a peptide derived from the central and -terminal regions of Aβ. In the crystal lattice, the peptide assembles to form two different dimers-an antiparallel β-sheet dimer and a parallel β-sheet dimer-that each further self-assemble to form two different tetramers-a sandwich-like tetramer and a twisted β-sheet tetramer. The structures of these dimers and tetramers derived from Aβ serve as potential models for dimers and tetramers of full-length Aβ that form and in Alzheimer's disease-afflicted brains.
寡聚物形成的高分辨率结构β-淀粉样肽，Aβ，对理解阿尔茨海默病的分子基础很重要。Aβ的二聚体与阿尔茨海默病的发病机制和进展有关，而 Aβ的四聚体具有神经毒性。本文报道了由 Aβ的中心和末端区域衍生的肽形成的二聚体、四聚体和八聚体的 X 射线晶体结构。在晶格中，肽组装形成两种不同的二聚体-反平行β-片层二聚体和平行β-片层二聚体-每个进一步自组装形成两种不同的四聚体-夹心样四聚体和扭曲β-片层四聚体。这些源自 Aβ的二聚体和四聚体的结构可作为全长 Aβ的二聚体和四聚体的潜在模型，全长 Aβ的二聚体和四聚体在阿尔茨海默病患者的大脑中形成。
