Kreutzer, Adam G. Spencer, Ryan K. McKnelly, Kate J. Yoo, Stan Hamza, Imane L. Salveson, Patrick J. Nowick, James S. A Hexamer of a Peptide Derived from Aβ<sub>16–36</sub> The absence of high-resolution structures of amyloid oligomers constitutes a major gap in our understanding of amyloid diseases. A growing body of evidence indicates that oligomers of the β-amyloid peptide Aβ are especially important in the progression of Alzheimer’s disease. In many Aβ oligomers, the Aβ monomer components are thought to adopt a β-hairpin conformation. This paper describes the design and study of a macrocyclic β-hairpin peptide derived from Aβ<sub>16–36</sub>. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis and size exclusion chromatography studies show that the Aβ<sub>16–36</sub> β-hairpin peptide assembles in solution to form hexamers, trimers, and dimers. X-ray crystallography reveals that the peptide assembles to form a hexamer in the crystal state and that the hexamer is composed of dimers and trimers. Lactate dehydrogenase release assays show that the oligomers formed by the Aβ<sub>16–36</sub> β-hairpin peptide are toxic toward neuronally derived SH-SY5Y cells. Replica-exchange molecular dynamics demonstrates that the hexamer can accommodate full-length Aβ. These findings expand our understanding of the structure, solution-phase behavior, and biological activity of Aβ oligomers and may offer insights into the molecular basis of Alzheimer’s disease. macrocyclic β- hairpin peptide;β- hairpin conformation;dimers;hexamer;size exclusion chromatography studies show;β oligomers;Alzheimer;SH-SY 5Y cells;understanding;trimer;β monomer components;β- amyloid peptide;Lactate dehydrogenase release assays show 2017-10-13
    https://acs.figshare.com/articles/journal_contribution/A_Hexamer_of_a_Peptide_Derived_from_A_sub_16_36_sub_/5545414
10.1021/acs.biochem.7b00831.s001