FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.
PR-39, a proline/arginine-rich peptide antibiotic, has been purified from pig intestine and later shown to originate in the bone marrow. Intending to isolate a clone for a human counterpart to PR-39, we synthesized a PCR probe derived from the PR-39 gene. However, when this probe was used to screen a human bone marrow cDNA library, eight clones were obtained with information for another putative human peptide antibiotic, designated FALL-39 after the first four residues. FALL-39 is a 39-residue peptide lacking cysteine and tryptophan. All human peptide antibiotics previously isolated (or predicted) belong to the defensin family and contain three disulfide bridges. The clone for prepro-FALL-39 encodes a cathelin-like precursor protein with 170 amino acid residues. We have postulated a dibasic processing site for the mature FALL-39 and chemically synthesized the putative peptide. In basal medium E, synthetic FALL-39 was highly active against Escherichia coli and Bacillus megaterium. Residues 13-34 in FALL-39 can be predicted to form a perfect amphiphatic helix, and CD spectra showed that medium E induced 30% helix formation in FALL-39. RNA blot analyses disclosed that the gene for FALL-39 is expressed mainly in human bone marrow and testis.
Agerberth
B
B
Department of Microbiology, Stockholm University, Sweden.
Gunne
H
H
Odeberg
J
J
Kogner
P
P
Boman
H G
HG
Gudmundsson
G H
GH
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism*; D002648:Child; D003001:Cloning, Molecular; D003545:Cysteine; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification; D017433:Protein Structure, Secondary; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013737:Testis / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D018076:DNA, Complementary; C091425:FALL 39; D010455:Peptides; D012333:RNA, Messenger; C072212:PR 39; D012313:RNA; D003545:Cysteine