Translocation Of The pAntp Peptide And Its Amphipathic Analogue Ap-2al

The pAntp peptide, corresponding to the third helix of the homeodomain of the
Antennapedia protein, enters by a receptor-independent process into eukaryotic
cells. The interaction between the pAntp peptide and the phospholipid matrix of
the plasma membrane seems to be the first step involved in the translocation
mechanism. However, the mechanism by which the peptide translocates through the
cell membrane is still not well established. We have investigated the
translocation ability of pAntp through a protein-free phospholipid membrane in
comparison with a more amphipathic analogue. We show by fluorescence
spectroscopy, circular dichroism, NMR spectroscopy, and molecular modeling that
pAntp is not sufficiently helically amphipathic to cross a phospholipid membrane
of a model system. Due to its primary sequence related to its DNA binding ability
in the Antennapedia homeodomain-DNA complex, the pAntp peptide does not belong to
the amphipathic alpha-helical peptide family whose members are able to
translocate by pore formation.