7U4P

Covalently stabilized triangular trimer composed of Abeta17-36 beta-hairpins

これはPDB形式変換不可エントリーです。

7U4P の概要

• エントリーDOI: 10.2210/pdb7u4p/pdb
• 分子名称: Amyloid-beta 17-36 peptide (2 entities in total)
• 機能のキーワード: abeta oligomer, beta-hairpin, trimer, dodecamer, alzheimer's disease, de novo protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 6643.88

構造登録者

Kreutzer, A.G.,Haerianardakani, S.,Nowick, J.S. (登録日: 2022-02-28, 公開日: 2023-03-15, 最終更新日: 2024-03-27)

主引用文献

Kreutzer, A.G.,Parrocha, C.M.T.,Haerianardakani, S.,Guaglianone, G.,Nguyen, J.T.,Diab, M.N.,Yong, W.,Perez-Rosendahl, M.,Head, E.,Nowick, J.S.
Antibodies Raised Against an A beta Oligomer Mimic Recognize Pathological Features in Alzheimer's Disease and Associated Amyloid-Disease Brain Tissue.
Acs Cent.Sci., 10:104-121, 2024

PubMed Abstract: Antibodies that target the β-amyloid peptide (Aβ) and its associated assemblies are important tools in Alzheimer's disease research and have emerged as promising Alzheimer's disease therapies. This paper reports the creation and characterization of a triangular Aβ trimer mimic composed of Aβ β-hairpins and the generation and study of polyclonal antibodies raised against the Aβ trimer mimic. The Aβ trimer mimic is covalently stabilized by three disulfide bonds at the corners of the triangular trimer to create a homogeneous oligomer. Structural, biophysical, and cell-based studies demonstrate that the Aβ trimer mimic shares characteristics with oligomers of full-length Aβ. X-ray crystallography elucidates the structure of the trimer and reveals that four copies of the trimer assemble to form a dodecamer. SDS-PAGE, size exclusion chromatography, and dynamic light scattering reveal that the trimer also forms higher-order assemblies in solution. Cell-based toxicity assays show that the trimer elicits LDH release, decreases ATP levels, and activates caspase-3/7 mediated apoptosis. Immunostaining studies on brain slices from people who lived with Alzheimer's disease and people who lived with Down syndrome reveal that the polyclonal antibodies raised against the Aβ trimer mimic recognize pathological features including different types of Aβ plaques and cerebral amyloid angiopathy.

PubMed: 38292607
DOI: 10.1021/acscentsci.3c00592

実験手法

X-RAY DIFFRACTION (1.803 Å)