The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.
The peptide FA-LL-37, previously termed FALL-39, was originally predicted from on ORF of a cDNA clone isolated from a human bone marrow library. This peptide was synthesized and found to have antibacterial activity. We have now characterized and sequenced the complete gene for FA-LL-37, termed FALL39. It is a compact gene of 1963 bp with four exons. Exons 1-3 code for a signal sequence and the cathelin region. Exon 4 contains the information for the mature antibacterial peptide. Our results indicate that FALL39 is the only member of the cathelin gene family present in the human genome. Potential binding sites for acute-phase-response factors are identified in the promoter and in intron 2. A possible role for the cytokine interleukin-6 in the regulation of FALL 39 is discussed. Anti-(FA-LL-37) IgG located the peptide in granulocytes and we isolated the mature peptide from these cells after degranulation. Structural analysis determined the mature peptide to be LL-37. To obtain LL-37 for antibacterial assays, synthetic FA-LL-37 was degraded with dipeptidyl-peptidase I. This analysis showed that mature LL-37 is a potent antibacterial peptide.
Gudmundsson
G H
GH
Department of Microbiology, Stockholm University, Sweden.
Agerberth
B
B
Odeberg
J
J
Bergman
T
T
Olsson
B
B
Salcedo
R
R
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000097:blood / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D015139:Blotting, Southern; D020789:Cathepsin C; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; C091425:FALL 39; D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; C084515:cathelin; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C