5W4J
X-ray crystallographic structure of a beta-hairpin peptide mimic. (ORN)KLV(MEA)FAE(ORN)AIIGLMV.
Summary for 5W4J
| Entry DOI | 10.2210/pdb5w4j/pdb |
| Descriptor | 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) |
| Functional Keywords | amyloid, oligomer, protein fibril, de novo protein |
| Biological source | Homo sapiens |
| Total number of polymer chains | 6 |
| Total formula weight | 10428.99 |
| Authors | Kreutzer, A.G.,Nowick, J.S. (deposition date: 2017-06-11, release date: 2017-11-22, Last modification date: 2020-01-01) |
| 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 Cited by 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: 29028351DOI: 10.1021/acs.biochem.7b00831 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.08 Å) |
Structure validation
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