PMC

Dynamics simulations of an apoE NMR structure for 300 ns. The N-terminal domain is shown in green, the C-terminal domain is shown in blue, and the hinge domain is shown in red. “Aggregation-prone” hot-spots ¹³²ERLVR¹³⁶ and ¹⁵⁸RLAVY¹⁶² are colored in orange. Structural movements uncover otherwise hidden apoE hot-spots (arrows). Models are represented in 0°, 90°, and 180°.

FT-IR spectra (1100–1800 cm⁻¹) derived from suspensions of fibrils, produced from (a) ¹³²ERLVR¹³⁶ and (b) ¹⁵⁸RLAVY¹⁶². Each apoE peptide cast on a flat stainless-steel plate and left to air-dry slowly at ambient conditions to form hydrated, thin films. Each film possesses a β-sheet conformation, as it is evident by the presence of strong amide I and II bands.

Experimental results of self-aggregation assays for apoE peptide–analogues. (a,b) Electron micrographs of typical amyloid fibrils, derived by self-assembly of (a) ¹³²ERLVR¹³⁶ and (b) ¹⁵⁸RLAVY¹⁶² “aggregation-prone” fragments. Scalebars for (a) ¹³²ERLVR¹³⁶ and (b) ¹⁵⁸RLAVY¹⁶² are 200 nm and 500 nm, respectively. (c,d) Photomicrographs of apoE peptide fibrils stained with the amyloid specific Congo red dye ((c) ¹³²ERLVR¹³⁶ and (d) ¹⁵⁸RLAVY¹⁶²). The apple-green birefringence, characteristic for all amyloid fibrillar materials, is clearly seen (Scale bar 500 μm).(e,f) X-ray diffraction patterns from oriented fibers of apoE “aggregation-prone” fragments, (e) ¹³²ERLVR¹³⁶ and (f) ¹⁵⁸RLAVY¹⁶².

Native nuclear magnetic resonance (NMR) structure of human mature apolipoprotein E (apoE) [] and apoE amyloidogenic profile by AMYLPRED []. (a) Different colors show all three structural domains of the apoE3 in solution: the N-terminal domain (green);the C-terminal domain (blue); and the hinge domain (red). Colored regions in orange illustrate “aggregation-prone” segments ¹³²ERLVR¹³⁶ and ¹⁵⁸RLAVY¹⁶², respectively, both located on the 4th helix of the four-helix bundle. (b) Amyloid propensity apoE histogram represents a weak overall amyloidogenicity, since only two segments exceed the consensus AMYLPRED threshold (regions ¹³²ERLVR¹³⁶ and ¹⁵⁸RLAVY¹⁶²). Color scheme follows the rules described in (a).