Amyloidogenic 60-71 deletion/ValThr insertion mutation of apolipoprotein A-I generates a new aggregation-prone segment that promotes nucleation through entropic effects.

ABSTRACT: The N-terminal fragment of apolipoprotein A-I (apoA-I), comprising residues 1-83, contains three segments prone to aggregation: residues 14-22, 53-58, and 67-72. We previously demonstrated that residues 14-22 are critical in apoA-I fibril formation while residues 53-58 entropically drove the nucleation process. Here, we investigated the impact of amyloidogenic mutations (Δ60-71/VT, Δ70-72, and F71Y) located around residues 67-72 on fibril formation by the apoA-I 1-83 fragment. Thioflavin T fluorescence assay demonstrated that the Δ60-71/VT mutation significantly enhances both nucleation and fibril elongation rates, whereas the Δ70-72 and F71Y mutations had minimal effects. Circular dichroism measurements and microscopic observations revealed that all variant fragments formed straight fibri

SUBMITTER: Namba N 

PROVIDER: S-EPMC10613298 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature