X-ray Crystallography Reveals Parallel and Antiparallel β-Sheet Dimers of a β-Hairpin Derived from Aβ(16-36) that Assemble to Form Different Tetramers.
X-ray Crystallography Reveals Parallel and Antiparallel β-Sheet Dimers of a β-Hairpin Derived from Aβ(16-36) that Assemble to Form Different Tetramers.
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DOI：
10.1021/acschemneuro.0c00290
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发表时间：
2020-08-05
影响因子：
5
通讯作者：
Nowick JS
中科院分区：
文献类型：
--
作者：
Kreutzer AG;Samdin TD;Guaglianone G;Spencer RK;Nowick JS
由β-淀粉样肽Aβ形成的寡聚体的高分辨率结构对于理解阿尔茨海默病的分子基础非常重要。Aβ的二聚体与阿尔茨海默病的发病机制和进展有关，Aβ的四聚体具有神经毒性。本文报道了Aβ中心和C端肽段形成的二聚体、四聚体和八聚体的X射线晶体学结构。在晶格中，肽组装形成两种不同的二聚体-反平行β折叠二聚体和平行β折叠二聚体-其各自进一步自组装形成两种不同的四聚体-类β折叠四聚体和扭曲β折叠四聚体。这些衍生自Aβ的二聚体和四聚体的结构可作为体外和阿尔茨海默病脑中形成的全长Aβ二聚体和四聚体的潜在模型。
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 C-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 in vitro and in Alzheimer’s disease brains.
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DOI：
10.1126/science.aao2825
发表时间：
2017-10-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gremer L;Schölzel D;Schenk C;Reinartz E;Labahn J;Ravelli RBG;Tusche M;Lopez-Iglesias C;Hoyer W;Heise H;Willbold D;Schröder GF
通讯作者：
Schröder GF
影响因子：
5.6
作者：
Huang, Danting;Zimmerman, Maxwell I.;Martin, Patricia K.;Nix, A. Jeremy;Rosenberry, Terrone L.;Paravastu, Anant K.
通讯作者：
Paravastu, Anant K.
影响因子：
15
作者：
Nowick, JS;Brower, JO
通讯作者：
Brower, JO
影响因子：
18.3
作者：
Kreutzer AG;Nowick JS
通讯作者：
Nowick JS
影响因子：
14.5
作者：
Brinkmalm, Gunnar;Hong, Wei;Walsh, Dominic M.
通讯作者：
Walsh, Dominic M.