Phenylalanine Mutation to Cyclohexylalanine Facilitates Triangular Trimer Formation by β-Hairpins Derived from Aβ.

ABSTRACT: Oligomers of the β-amyloid peptide, Aβ, play a central role in the pathogenesis and progression of Alzheimer's disease. Trimers and higher-order oligomers composed of trimers are thought to be the most neurotoxic Aβ oligomers. To gain insights into the structure and assembly of Aβ oligomers, our laboratory has previously designed and synthesized macrocyclic peptides derived from Aβ_17-23 and Aβ_30-36 that fold to form β-hairpins and assemble to form trimers. In this study, we found that mutating Phe₂₀ to cyclohexylalanine (Cha) in macrocyclic Aβ-derived peptides promotes crystallization of an Aβ-derived peptide containing the Aβ_24-29 loop (peptide 3_F20Cha) and permits elucidation of its structure and assembly by X-ray cryst

SUBMITTER: Haerianardakani S 

PROVIDER: S-EPMC7821965 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature