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.
Drin
G
G
Synt:em, Parc Scientifique Georges Besse, 30000 Nîmes, France.
Déméné
H
H
Temsamani
J
J
Brasseur
R
R
D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001692:Biological Transport; D002942:Circular Dichroism; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D008051:Lipid Bilayers; D009687:Nuclear Proteins; D010455:Peptides; C493674:TfAP-2 protein, Drosophila; D050656:Transcription Factor AP-2; D014157:Transcription Factors