作者
Adam G Kreutzer, Chelsea Marie T Parrocha, Sepehr Haerianardakani, Gretchen Guaglianone, Jennifer T Nguyen, Michelle N Diab, William Yong, Mari Perez-Rosendahl, Elizabeth Head, James S Nowick
发表日期
2023/12/21
期刊
ACS Central Science
卷号
10
期号
1
页码范围
104-121
出版商
American Chemical Society
简介
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 Aβ17–36 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 …
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AG Kreutzer, CMT Parrocha, S Haerianardakani… - ACS Central Science, 2023