7JXN

Beta hairpin derived from Abeta17-36 with an F20Cha mutation

7JXN の概要

• エントリーDOI: 10.2210/pdb7jxn/pdb
• 分子名称: Amyloid-beta 17-36 peptide, CHLORIDE ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: amyloid, oligomer, alzheimer's disease, beta-hairpin, de novo protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 8888.40

構造登録者

Kreutzer, A.G.,Haerianardakani, S.,Nowick, J.S. (登録日: 2020-08-27, 公開日: 2020-12-09, 最終更新日: 2020-12-23)

主引用文献

Haerianardakani, S.,Kreutzer, A.G.,Salveson, P.J.,Samdin, T.D.,Guaglianone, G.E.,Nowick, J.S.
Phenylalanine Mutation to Cyclohexylalanine Facilitates Triangular Trimer Formation by beta-Hairpins Derived from A beta.
J.Am.Chem.Soc., 142:20708-20716, 2020

PubMed Abstract: Oligomers of the β-amyloid peptide, Aβ, play a central role in the pathogenesis and progression of Alzheimer's disease. Trimers and higher-order oligomers composed of trimers are thought to be the most neurotoxic Aβ oligomers. To gain insights into the structure and assembly of Aβ oligomers, our laboratory has previously designed and synthesized macrocyclic peptides derived from Aβ and Aβ that fold to form β-hairpins and assemble to form trimers. In this study, we found that mutating Phe to cyclohexylalanine (Cha) in macrocyclic Aβ-derived peptides promotes crystallization of an Aβ-derived peptide containing the Aβ loop (peptide ) and permits elucidation of its structure and assembly by X-ray crystallography. X-ray crystallography shows that peptide forms a hexamer. X-ray crystallography and SDS-PAGE further show that trimer , a covalently stabilized trimer derived from peptide , forms a dodecamer. Size exclusion chromatography shows that trimer forms higher-order assemblies in solution. Trimer exhibits cytotoxicity against the neuroblastoma cell line SH-SY5Y. These studies demonstrate the use of the F20Cha mutation to further stabilize oligomers of Aβ-derived peptides that contain more of the native sequence and thus better mimic the oligomers formed by full-length Aβ.

PubMed: 33237748
DOI: 10.1021/jacs.0c09281

実験手法

X-RAY DIFFRACTION (2 Å)