The N-terminal 12 residue long peptide of HIV gp41 is the minimal peptide sufficient to induce significant T-cell-like membrane destabilization in vitro.
[en] Here, we predicted the minimal N-terminal fragment of gp41 required to induce
significant membrane destabilization using IMPALA. This algorithm is dedicated to
predict peptide interaction with a membrane. We based our prediction of the
minimal fusion peptide on the tilted peptide theory. This theory proposes that
some protein fragments having a peculiar distribution of hydrophobicity adopt a
tilted orientation at a hydrophobic/hydrophilic interface. As a result of this
orientation, tilted peptides should disrupt the interface. We analysed in silico
the membrane-interacting properties of gp41 N-terminal peptides of different
length derived from the isolate BRU and from an alignment of 710 HIV strains
available on the Los Alamos National Laboratory. Molecular modelling results
indicated that the 12 residue long peptide should be the minimal fusion peptide.
We then assayed lipid-mixing and leakage of T-cell-like liposomes with N-terminal
peptides of different length as first challenge of our predictions. Experimental
results confirmed that the 12 residue long peptide is necessary and sufficient to
induce membrane destabilization to the same extent as the 23 residue long fusion
peptide. In silico analysis of some fusion-incompetent mutants presented in the
literature further revealed that they cannot insert into a modelled membrane
correctly tilted. According to this work, the tilted peptide model appears to
explain at least partly the membrane destabilization properties of HIV fusion
peptide.
Thomas, Annick ; Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér.
Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech
Langue du document :
Anglais
Titre :
The N-terminal 12 residue long peptide of HIV gp41 is the minimal peptide sufficient to induce significant T-cell-like membrane destabilization in vitro.
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