Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein

Biochim Biophys Acta. 2008 Oct;1778(10):2127-37. doi: 10.1016/j.bbamem.2008.05.002. Epub 2008 May 11.

Abstract

Given their high alanine and glycine levels, plaque formation, alpha-helix to beta-sheet interconversion and fusogenicity, FP (i.e., the N-terminal fusion peptide of HIV-1 gp41; 23 residues) and amyloids were proposed as belonging to the same protein superfamily. Here, we further test whether FP may exhibit 'amyloid-like' characteristics, by contrasting its structural and functional properties with those of Abeta(26-42), a 17-residue peptide from the C-terminus of the amyloid-beta protein responsible for Alzheimer's. FTIR spectroscopy, electron microscopy, light scattering and predicted amyloid structure aggregation (PASTA) indicated that aqueous FP and Abeta(26-42) formed similar networked beta-sheet fibrils, although the FP fibril interactions were weaker. FP and Abeta(26-42) both lysed and aggregated human erythrocytes, with the hemolysis-onsets correlated with the conversion of alpha-helix to beta-sheet for each peptide in liposomes. Congo red (CR), a marker of amyloid plaques in situ, similarly inhibited either FP- or Abeta(26-42)-induced hemolysis, and surface plasmon resonance indicated that this may be due to direct CR-peptide binding. These findings suggest that membrane-bound beta-sheets of FP may contribute to the cytopathicity of HIV in vivo through an amyloid-type mechanism, and support the classification of HIV-1 FP as an 'amyloid homolog' (or 'amylog').

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides* / chemistry
  • Amyloid beta-Peptides* / metabolism
  • Coloring Agents / metabolism
  • Congo Red / metabolism
  • Erythrocytes / cytology
  • Erythrocytes / metabolism
  • HIV Envelope Protein gp41* / chemistry
  • HIV Envelope Protein gp41* / metabolism
  • HIV-1 / chemistry
  • Hemolysis
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments* / chemistry
  • Peptide Fragments* / metabolism
  • Protein Structure, Secondary*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Amyloid beta-Peptides
  • Coloring Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Congo Red