Cloning of the cDNA of a human neutrophil bactericidal protein. Structural and functional correlations.
The bactericidal permeability increasing protein (BPI) is a 50-60-kDa membrane-associated protein isolated from granules of polymorphonuclear leukocytes. A full-length cDNA clone encoding human BPI has been isolated and the derived amino acid sequence reveals a structure that is consistent with previously determined biological properties. BPI may be organized into two domains: the amino-terminal half, previously shown to contain all known antimicrobial activity, contains a large fraction of basic and hydrophilic residues. In contrast, the carboxyl-terminal half contains more acidic than basic residues and includes several potential transmembrane regions which may anchor the holoprotein in the granule membrane. The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic aminoterminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial envelope. The amino-terminal end of BPI exhibits significant similarity with the sequence of a rabbit lipopolysaccharide-binding protein, suggesting that both molecules share a similar structure for binding lipopolysaccharides.
Gray
P W
PW
Department of Developmental Biology, Genetech, Inc., South Francisco, California 94080.
Flaggs
G
G
Leong
S R
SR
Gumina
R J
RJ
Weiss
J
J
Ooi
C E
CE
Elsbach
P
P
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000235:genetics* / Q000302:isolation & purification; D002460:Cell Line; D003001:Cloning, Molecular; D003603:Cytotoxins / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004247:DNA / Q000302:isolation & purification*; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000032:analysis*; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D003603:Cytotoxins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D004247:DNA