Molecular modeling of apoE in complexes with Alzheimer's amyloid-β fibrils from human brain suggests a structural basis for apolipoprotein co-deposition with amyloids.

ABSTRACT: Apolipoproteins co-deposit with amyloids, yet apolipoprotein-amyloid interactions are enigmatic. To understand how apoE interacts with Alzheimer's amyloid-β (Aβ) peptide in fibrillary deposits, the NMR structure of full-length human apoE was docked to four structures of patient-derived Aβ_1-40 and Aβ_1-42 fibrils determined previously using cryo-electron microscopy or solid-state NMR. Similar docking was done using the NMR structure of human apoC-III. In all complexes, conformational changes in apolipoproteins were required to expose large hydrophobic faces of their amphipathic α-helices for sub-stoichiometric binding to hydrophobic surfaces on sides or ends of fibrils. Basic residues flanking the hydrophobic helical faces in apolipoproteins interacted favorably with ac

SUBMITTER: Lewkowicz E 

PROVIDER: S-EPMC11061799 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature