Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein.
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').
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Larry M
LM
Gordon
Alex
A
Nisthal
Andy B
AB
Lee
Sepehr
S
Eskandari
Piotr
P
Ruchala
Chun-Ling
CL
Jung
Alan J
AJ
Waring
Patrick W
PW
Mobley
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D003224:Congo Red / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D003224:Congo Red