FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.

1995/01/03 by B. Agerberth, B Agerberth, Hans Gunne +9 · 29 citations
Immunology and Microbiology · Medicine · Biochemistry, Genetics and Molecular Biology · #Antimicrobial Peptides and Activities #Peptidase Inhibition and Analysis #Biochemical and Structural Characterization

paper · doi:10.1073/pnas.92.1.195

Abstract

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.

Cited by

• Amphipathic, α-helical antimicrobial peptides
• Temporins, Antimicrobial Peptides from the European Red Frog <i>Rana temporaria</i>
• Ll-37, the Neutrophil Granule–And Epithelial Cell–Derived Cathelicidin, Utilizes Formyl Peptide Receptor–Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells
• Charge-dependent insertion of the antimicrobial peptide magainin 2 into lipid monolayers probed by neutron reflectivity
• Apoptosis of airway epithelial cells: human serum sensitive induction by the cathelicidin LL-37. [europepmc]
• Defensins and other antimicrobial peptides at the ocular surface. [europepmc]
• Antimicrobial peptides and the skin immune defense system. [europepmc]
• The vitamin D pathway: a new target for control of the skin's immune response? [europepmc]
• Tumors sound the alarmin(s). [europepmc]
• Leucine leucine-37 uses formyl peptide receptor-like 1 to activate signal transduction pathways, stimulate oncogenic gene expression, and enhance the invasiveness of ovarian cancer cells. [europepmc]
• The vitamin D-antimicrobial peptide pathway and its role in protection against infection. [europepmc]
• The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. [europepmc]
• Staphylococcus colonization of the skin and antimicrobial peptides. [europepmc]
• Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide. [europepmc]
• Implications of the innate immune response to adenovirus and adenoviral vectors. [europepmc]
• Antimicrobial peptides: old molecules with new ideas. [europepmc]
• Cathelicidin-related antimicrobial peptide is required for effective lung mucosal immunity in Gram-negative bacterial pneumonia. [europepmc]
• High-quality 3D structures shine light on antibacterial, anti-biofilm and antiviral activities of human cathelicidin LL-37 and its fragments. [europepmc]
• Human antimicrobial peptides and proteins. [europepmc]
• The Human Cathelicidin Antimicrobial Peptide LL-37 and Mimics are Potential Anticancer Drugs. [europepmc]
• Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans. [europepmc]
• Design and Application of Antimicrobial Peptide Conjugates. [europepmc]
• Biophysical Investigations Elucidating the Mechanisms of Action of Antimicrobial Peptides and Their Synergism. [europepmc]
• Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. [europepmc]
• Human Antimicrobial Peptides as Therapeutics for Viral Infections. [europepmc]
• Significance of LL-37 on Immunomodulation and Disease Outcome. [europepmc]
• Nanotechnology-Based Delivery Systems for Antimicrobial Peptides. [europepmc]
• Immunomodulatory and Allergenic Properties of Antimicrobial Peptides. [europepmc]
• Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics. [europepmc]

Related

• Anti‐microbial peptides: from invertebrates to vertebrates
• Antimicrobial peptides: Application informed by evolution
• Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity
• Discovery of antimicrobial peptides in the global microbiome with machine learning
• Ll-37, the Neutrophil Granule–And Epithelial Cell–Derived Cathelicidin, Utilizes Formyl Peptide Receptor–Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells