The specificity of Sushi peptides for endotoxin and anionic phospholipids: potential application of POPG as an adjuvant for anti-LPS strategies.
Sushi peptides [S1 (Sushi 1 peptide) and S3] are derived from the LPS (lipopolysaccharide; also known as endotoxin)-binding domains of an LPS-sensitive serine protease, Factor C, from the horseshoe crab (Carcinoscorpius rotundicauda). S1 and S3 interact at high affinity with LPS. The intermolecular disulphide bonding in the S3 dimer is indispensable for its LPS binding, disruption and consequent neutralization. Simultaneously, the specific interaction between the Sushi peptides and bacterial membrane phospholipids further explains the selective propensity of these peptides for the gram-negative bacteria. Our findings yield insights into a complex molecular paradigm in which the juxtaposition of LPS molecules and the anionic phospholipid POPG (1-palmitoyl-2-oleoyl phosphatidylglycerol) on the bacterial outer membrane confers such interfacial properties which create the optimal environment for the interaction between the peptides and bacterial membrane lipids.
Li
P
P
Department of Biological Sciences, National University of Singapore, Singapore 117543.
Sun
M
M
Ho
B
B
Ding
J L
JL
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000737:chemistry; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry; D013379:Substrate Specificity
D000277:Adjuvants, Pharmaceutic; D000838:Anions; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010455:Peptides; D010715:Phosphatidylglycerols; D010743:Phospholipids; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D012697:Serine Endopeptidases