7JQR
Abeta 16-36 beta-hairpin mimic with E22G Arctic mutation
Summary for 7JQR
| Entry DOI | 10.2210/pdb7jqr/pdb |
| Descriptor | Abeta 16-36 beta-hairpin mimic VAL-ORN-LYS-LEU-VAL-MEA-PHE-ALA-GLY-ORN-ALA-ILE-ILE-GLY-LEU-MET, IODIDE ION (3 entities in total) |
| Functional Keywords | alzheimer's disease, amyloid, abeta, oligomer, familial mutant, de novo protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 2102.92 |
| Authors | Kreutzer, A.G.,McKnelly, K.J.,Nowick, J.S. (deposition date: 2020-08-11, release date: 2021-09-08, Last modification date: 2022-03-30) |
| Primary citation | McKnelly, K.J.,Kreutzer, A.G.,Howitz, W.J.,Haduong, K.,Yoo, S.,Hart, C.,Nowick, J.S. Effects of Familial Alzheimer's Disease Mutations on the Assembly of a beta-Hairpin Peptide Derived from A beta 16-36 . Biochemistry, 61:446-454, 2022 Cited by PubMed Abstract: Familial Alzheimer's disease (FAD) is associated with mutations in the β-amyloid peptide (Aβ) or the amyloid precursor protein (APP). FAD mutations of Aβ were incorporated into a macrocyclic peptide that mimics a β-hairpin to study FAD point mutations K16N, A21G, E22Δ, E22G, E22Q, E22K, and L34V and their effect on assembly, membrane destabilization, and cytotoxicity. The X-ray crystallographic structures of the four E22 mutant peptides reveal that the peptides assemble to form the same compact hexamer. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) experiments reveal that the mutant FAD peptides assemble as trimers or hexamers, with peptides that have greater positive charge assembling as more stable hexamers. Mutations that increase the positive charge also increase the cytotoxicity of the peptides and their propensity to destabilize lipid membranes. PubMed: 35213141DOI: 10.1021/acs.biochem.1c00664 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.07 Å) |
Structure validation
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