Apolipoprotein E4 has extensive conformational heterogeneity in lipid-free and lipid-bound forms.

ABSTRACT: The ε4-allele variant of apolipoprotein E (ApoE4) is the strongest genetic risk factor for Alzheimer's disease, although it only differs from its neutral counterpart ApoE3 by a single amino acid substitution. While ApoE4 influences the formation of plaques and neurofibrillary tangles, the structural determinants of pathogenicity remain undetermined due to limited structural information. Previous studies have led to conflicting models of the C-terminal region positioning with respect to the N-terminal domain across isoforms largely because the data are potentially confounded by the presence of heterogeneous oligomers. Here, we apply a combination of single-molecule spectroscopy and molecular dynamics simulations to construct an atomically detailed model of monomeric ApoE4 and probe the effe

SUBMITTER: Stuchell-Brereton MD 

PROVIDER: S-EPMC9963066 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature