Structural and functional organization of the human neutrophil 60 kDa bactericidal/permeability-increasing protein.
We have isolated, after limited proteolysis of the bactericidal/permeability-increasing protein (BPI) of human polymorphonuclear leukocytes (PMN), two fragments representing roughly the two halves of the BPI molecule. The 25 kDa N-terminal fragment possesses all the antibacterial activities of the 60 kDa parent protein, while the ca. 30 kDa C-terminal fragment has no detectable activity. The 25 kDa fragment is as potent on a molar basis as holo-human BPI against rough Escherichia coli, is more potent than holo-BPI against more resistant smooth E. coli, and retains the specificity of BPI toward Gram-negative bacteria. The findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the N-terminal half of the molecule, implying a novel structural/functional organization for a cytotoxic protein.
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Department of Medicine, New York University School of Medicine, NY 10016.
Weiss
J
J
Elsbach
P
P
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology; D004926:Escherichia coli; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry; D008565:Membrane Proteins; D009504:Neutrophils / Q000737:chemistry*; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology; D010539:Permeability
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010446:Peptide Fragments; C021623:bactericidal permeability increasing protein