The extreme N-terminal region of human apolipoprotein A-I has a strong propensity to form amyloid fibrils

FEBS Lett. 2014 Jan 31;588(3):389-94. doi: 10.1016/j.febslet.2013.11.031. Epub 2013 Dec 5.

Abstract

The N-terminal 1-83 residues of apolipoprotein A-I (apoA-I) have a strong propensity to form amyloid fibrils, in which the 46-59 segment was reported to aggregate to form amyloid-like fibrils. In this study, we demonstrated that a fragment peptide comprising the extreme N-terminal 1-43 residues strongly forms amyloid fibrils with a transition to β-sheet-rich structure, and that the G26R point mutation enhances the fibril formation of this segment. Our results suggest that in addition to the 46-59 segment, the extreme N-terminal region plays a crucial role in the development of amyloid fibrils by the N-terminal fragment of amyloidogenic apoA-I variants.

Keywords: AFM; ATR; Amyloid fibril; Apolipoprotein A-I; FTIR; HDL; Peptide; Point mutation; ThT; WMF; apoA-I; apolipoprotein A-I; atomic force microscopy; attenuated total reflection; fourier transform infrared spectroscopy; high-density lipoprotein; thioflavinT; wavelength of maximum fluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / biosynthesis*
  • Amyloid / chemistry
  • Amyloid / genetics
  • Apolipoprotein A-I / biosynthesis*
  • Apolipoprotein A-I / chemistry
  • Apolipoprotein A-I / genetics*
  • Circular Dichroism
  • Humans
  • Microscopy, Atomic Force
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Point Mutation
  • Protein Conformation
  • Protein Structure, Secondary
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Amyloid
  • Apolipoprotein A-I
  • Peptide Fragments