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Publication Abstract from PubMed

Familial Alzheimer's disease (FAD) is associated with mutations in the beta-amyloid peptide (Abeta) or the amyloid precursor protein (APP). FAD mutations of Abeta were incorporated into a macrocyclic peptide that mimics a beta-hairpin to study FAD point mutations K16N, A21G, E22Delta, 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.

Effects of Familial Alzheimer's Disease Mutations on the Assembly of a beta-Hairpin Peptide Derived from Abeta16-36.,McKnelly KJ, Kreutzer AG, Howitz WJ, Haduong K, Yoo S, Hart C, Nowick JS Biochemistry. 2022 Mar 15;61(6):446-454. doi: 10.1021/acs.biochem.1c00664. Epub, 2022 Feb 25. PMID:35213141^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.