Membrane thinning effect of the beta-sheet antimicrobial protegrin.
Lipid bilayers containing the antimicrobial peptide protegrin-1 (PG-1) were studied by lamellar X-ray diffraction. Previously, we have shown that the peptide exists in two distinct states when associated with lipid bilayers depending on the peptide concentration [Heller, W. T., Waring, A. J., Lehrer, R. I., and Huang, H. W. (1998) Biochemistry 37, 17331-17338]. For concentrations below a lipid-dependent threshold, PG-1 exhibits a unique oriented circular dichroism spectrum called the S state. X-ray experiments show that in this state PG-1 decreases the thickness of the lipid bilayer in proportion to the peptide concentration, similar to alamethicin's membrane thinning effect. This indicates that the S state is adsorbed in the headgroup region of the lipid bilayer, where the peptide is in an inactive state. For PG-1 above the threshold concentration, X-ray diffraction shows that the interaction between the peptide and the bilayer changes significantly. These results suggest that PG-1 has the same concentration-gated mechanism of action as alamethicin.
Heller
W T
WT
Department of Physics, Rice University, Houston, Texas 77251, USA.
Waring
A J
AJ
Lehrer
R I
RI
Harroun
T A
TA
Weiss
T M
TM
Yang
L
L
Huang
H W
HW
D000408:Alamethicin / Q000737:chemistry; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D011506:Proteins; C094880:protegrin-1; D000408:Alamethicin; C021016:1,2-diphytanoylphosphatidylcholine