TI  - Molecular determinants of the interaction between the C-terminal domain of
      Alzheimer's  <prot>beta-amyloid peptide</prot>  and  <prot>apolipoprotein E</prot> alpha -helices.
PG  - 758-69
AB  - In a previous work, we predicted and demonstrated that the 29-42-residue
      fragment of <prot>beta-amyloid peptide</prot> (<prot>Abeta peptide</prot>) has in vitro capacities
      close to those of the tilted fragment of viral fusion proteins. We further
      demonstrated that  <prot>apolipoprotein E2</prot>  and  E3  but not <prot>apolipoprotein E4</prot> can
      decrease the fusogenic activity of  <prot>Abeta</prot>  (29-42) via a direct interaction.
      Therefore, we suggested that this fragment is implicated in the
      neurotoxicity of <prot>Abeta</prot> and in the protective effects of <prot>apolipoprotein E</prot>
      in Alzheimer's disease. Because structurally related apolipoproteins do
      not interact with the <prot>Abeta</prot> C-terminal domain but inhibit viral fusion, we
      suggested that interactions existing between fusogenic peptides and
      apolipoproteins are selective and responsible for the inhibition of
      fusion. In this study, we simulated interactions of all amphipathic
      helices of <prot>apolipoproteins E</prot> and A-I with <prot>Abeta</prot> and simian
      immunodeficiency virus (SIV) fusogenic fragments by molecular modeling. We
      further calculated cross-interactions that do not inhibit fusion in vitro.
      The results suggest that interactions of hydrophobic residues are the
      major event to inhibit the fusogenic capacities of <prot>Abeta</prot>(29-42) and SIV
      peptides. Selectivity of those interactions is due to the steric
      complementarity between bulky hydrophobic residues in the fusogenic
      fragments and hydrophobic residues in the apolipoprotein C-terminal
      amphipathic helices.
AD  - INSERM U. 10, Hopital Bichat-Claude Bernard, Paris, France.
