A 25-kDa NH2-terminal fragment carries all the antibacterial activities 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 neutrophils, a 25-kDa fragment that possesses the bactericidal and envelope-altering activities of the 60-kDa parent protein. On a molar basis, the fragment is as potent 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. NH2-terminal amino acid sequence analysis shows that the fragment is derived from the NH2 terminus of the BPI molecule. These findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the NH2-terminal 25-kDa segment, implying a novel structural/functional organization for a cytotoxic protein.
Ooi
C E
CE
Department of Medicine, New York University School of Medicine, New York 10016.
Weiss
J
J
Elsbach
P
P
Frangione
B
B
Mannion
B
B
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000302:isolation & purification* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins; D008970:Molecular Weight; D009504:Neutrophils / Q000502:physiology*; D010743:Phospholipids / Q000097:blood
D000596:Amino Acids; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D010743:Phospholipids; C021623:bactericidal permeability increasing protein