5W4I

X-ray crystallographic structure of a beta-hairpin peptide mimic derived from Abeta 16-36. Rigaku data set. (ORN)KLV(MEA)FAE(ORN)AIIGLMV.

Summary for 5W4I

• Entry DOI: 10.2210/pdb5w4i/pdb
• Descriptor: A-beta 17_36: ORN-LYS-LEU-VAL-MEA-PHE-ALA-GLU-ORN-ALA-ILE-ILE-GLY-LEU-MET-VAL, CHLORIDE ION, IODIDE ION, ... (4 entities in total)
• Functional Keywords: amyloid, oligomer, alzheimer's, trimer, protein fibril, de novo protein
• Biological source: Homo sapiens
• Total number of polymer chains: 3
• Total formula weight: 6123.69

Authors

Kreutzer, A.G.,McKnelly, K.J.,Nowick, J.S. (deposition date: 2017-06-11, release date: 2017-11-22, Last modification date: 2025-04-02)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.026 Å)