5W4J

X-ray crystallographic structure of a beta-hairpin peptide mimic. (ORN)KLV(MEA)FAE(ORN)AIIGLMV.

5W4J の概要

• エントリーDOI: 10.2210/pdb5w4j/pdb
• 分子名称: A-beta 17_36 peptide: ORN-LYS-VAL-PHE-MEA-ALA-ALA-ASP-ORN-ALA-ILE-ILE-GLY-LEU-MET-VAL (2 entities in total)
• 機能のキーワード: amyloid, oligomer, protein fibril, de novo protein
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 10428.99

構造登録者

Kreutzer, A.G.,Nowick, J.S. (登録日: 2017-06-11, 公開日: 2017-11-22, 最終更新日: 2020-01-01)

主引用文献

Kreutzer, A.G.,Spencer, R.K.,McKnelly, K.J.,Yoo, S.,Hamza, I.L.,Salveson, P.J.,Nowick, J.S.
A Hexamer of a Peptide Derived from A beta 16-36.
Biochemistry, 56:6061-6071, 2017

PubMed Abstract: 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. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size exclusion chromatography studies show that the Aβ 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 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.

PubMed: 29028351
DOI: 10.1021/acs.biochem.7b00831

実験手法

X-RAY DIFFRACTION (2.08 Å)