Headgroup structure and fatty acid chain length of the acidic phospholipids modulate the interaction of membrane mimetic vesicles with the antimicrobial peptide protegrin-1.
The interaction of protegrin-1 (PG-1), a small beta-sheet antimicrobial peptide with acidic phospholipid model membranes was investigated by differential scanning calorimetry. We found that PG-1 can distinguish between liposomes of the anionic phospholipids DPPG, DPPS and DPPA, eventhough the headgroups of these phospholipids all have the same net charge and they carry the same hydrocarbon chains. Specifically, PG-1 had only a minor effect on the thermotropic phase behavior of DPPA liposomes, while it interacted preferentially with the fluid phase of DPPS. Furthermore, PG-1 could induce a phase separation in DPPG liposomes resulting in the formation of peptide-rich domains even at low concentrations of the peptide. However, this peptide-rich domain was not evident when the fatty acyl chains were longer or shorter by two carbon atoms. In addition, PG-1 can also form peptide-rich domains in DPPS vesicles but only at high concentrations of the peptide. These results suggest that in addition to an overall negative charge, the structural features of the phospholipid headgroups, lipid packing and thus membrane fluidity will influence the interaction with PG-1, thereby modulating its biological activity.
Jing
Weiguo
W
Institute of Biophysics and X-ray Structure Research, Austrian Academy of Sciences, Graz.
Prenner
Elmar J
EJ
Vogel
Hans J
HJ
Waring
Alan J
AJ
Lehrer
Robert I
RI
Lohner
Karl
K
D000143:Acids / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D002152:Calorimetry, Differential Scanning; D005227:Fatty Acids / Q000737:chemistry*; D008081:Liposomes; D018716:Molecular Mimicry; D010743:Phospholipids / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D000143:Acids; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D005227:Fatty Acids; D008081:Liposomes; D010743:Phospholipids; D011506:Proteins; C094880:protegrin-1