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Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver.
- Source :
-
Protein science : a publication of the Protein Society [Protein Sci] 2003 Jan; Vol. 12 (1), pp. 143-52. - Publication Year :
- 2003
-
Abstract
- The human genome contains numerous genes whose protein products are unknown in terms of structure, interaction partner, expression, and function. To unravel the function of these orphan genes, it is of particular value to isolate native forms of protein and peptide products derived from these genes. From human blood ultrafiltrate, we characterized a novel gene-encoded, cysteine-rich, and cationic peptide that we termed liver-expressed antimicrobial peptide 2 (LEAP-2). We identified several circulating forms of LEAP-2 differing in their amino-terminal length, all containing a core structure with two disulfide bonds formed by cysteine residues in relative 1-3 and 2-4 positions. Molecular cloning of the cDNA showed that LEAP-2 is synthesized as a 77-residue precursor, which is predominantly expressed in the liver and highly conserved among mammals. This makes it a unique peptide that does not exhibit similarity with any known human peptide regarding its primary structure, disulfide motif, and expression. Analysis of the LEAP-2 gene resulted in the identification of an alternative promoter and at least four different splicing variants, with the two dominating transcripts being tissue-specifically expressed. The largest native LEAP-2 form of 40 amino acid residues is generated from the precursor at a putative cleavage site for a furin-like endoprotease. In contrast to smaller LEAP-2 variants, this peptide exhibited dose-dependent antimicrobial activity against selected microbial model organisms. LEAP-2 shares some characteristic properties with classic peptide hormones and it is expected that the isolation of this novel peptide will help to unravel its physiological role.
- Subjects :
- Alternative Splicing
Amino Acid Sequence
Animals
Anti-Infective Agents isolation & purification
Anti-Infective Agents pharmacology
Antimicrobial Cationic Peptides genetics
Antimicrobial Cationic Peptides isolation & purification
Antimicrobial Cationic Peptides pharmacology
Base Sequence
Blood Proteins genetics
Blood Proteins isolation & purification
Blood Proteins pharmacology
Cloning, Molecular
DNA, Complementary genetics
Disulfides chemistry
Dose-Response Relationship, Drug
Hemofiltration
Humans
Microbial Sensitivity Tests
Molecular Sequence Data
Organ Specificity
Saccharomyces cerevisiae drug effects
Sequence Alignment
Spectrometry, Mass, Electrospray Ionization
Anti-Infective Agents chemistry
Antimicrobial Cationic Peptides chemistry
Blood Proteins chemistry
Liver metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0961-8368
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Protein science : a publication of the Protein Society
- Publication Type :
- Academic Journal
- Accession number :
- 12493837
- Full Text :
- https://doi.org/10.1110/ps.0213603