Abstract
The first cyclic peptide discovered in animals is an antimicrobial octadecapeptide that is expressed in leukocytes of rhesus monkeys. The peptide, termed rhesus θdefensin 1 (RTD-1) is the prototype of a new family of antimicrobial peptides, which like the previously characterized α and βdefensin families, possesses broad spectrum microbicidal activities against bacteria, fungi, and protects mononuclear cells from infection by HIV-1. The cyclic θdefensin structure is essential for a number of its antimicrobial properties, as demonstrated by the markedly reduced microbicidal activities of de-cyclized θdefensin analogs. Genetic and biochemical experiments disclosed that the biosynthesis of RTD-1 results from the head-to-tail joining of two nine-amino acid peptides, each of which is donated by a separate precursor polypeptide, which are in fact C-terminally truncated pro-αdefensins. Alternate combinations of the two nonapeptides generate two additional macaque θdefensins, RTD-2 and RTD-3. Humans do not express θdefensin peptides, but mRNAs encoding at least two θdefensins are expressed in human bone marrow. However, in each case the open reading frame is interrupted by a stop codon in the signal peptide-coding region. The mature θdefensin peptide is a two-stranded βsheet that, like the α and βdefensins, is stabilized by three disulfides. However, the parallel orientation of the θ defensin disulfide arrangement allows for substantial flexibility around its short axis. Unlike α- and βdefensins, RTD-1 lacks an amphiphilic topology. This may partially explain the unusual interaction between θdefensins and phospholipid bilayers.
Keywords: theta-defensins, macrocyclic, cyclic peptides, antimicrobial
Current Protein & Peptide Science
Title: θ-Defensins: Cyclic Antimicrobial Peptides Produced by Binary Ligation of Truncated α-Defensins
Volume: 5 Issue: 5
Author(s): Michael E. Selsted
Affiliation:
Keywords: theta-defensins, macrocyclic, cyclic peptides, antimicrobial
Abstract: The first cyclic peptide discovered in animals is an antimicrobial octadecapeptide that is expressed in leukocytes of rhesus monkeys. The peptide, termed rhesus θdefensin 1 (RTD-1) is the prototype of a new family of antimicrobial peptides, which like the previously characterized α and βdefensin families, possesses broad spectrum microbicidal activities against bacteria, fungi, and protects mononuclear cells from infection by HIV-1. The cyclic θdefensin structure is essential for a number of its antimicrobial properties, as demonstrated by the markedly reduced microbicidal activities of de-cyclized θdefensin analogs. Genetic and biochemical experiments disclosed that the biosynthesis of RTD-1 results from the head-to-tail joining of two nine-amino acid peptides, each of which is donated by a separate precursor polypeptide, which are in fact C-terminally truncated pro-αdefensins. Alternate combinations of the two nonapeptides generate two additional macaque θdefensins, RTD-2 and RTD-3. Humans do not express θdefensin peptides, but mRNAs encoding at least two θdefensins are expressed in human bone marrow. However, in each case the open reading frame is interrupted by a stop codon in the signal peptide-coding region. The mature θdefensin peptide is a two-stranded βsheet that, like the α and βdefensins, is stabilized by three disulfides. However, the parallel orientation of the θ defensin disulfide arrangement allows for substantial flexibility around its short axis. Unlike α- and βdefensins, RTD-1 lacks an amphiphilic topology. This may partially explain the unusual interaction between θdefensins and phospholipid bilayers.
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Cite this article as:
Selsted E. Michael, θ-Defensins: Cyclic Antimicrobial Peptides Produced by Binary Ligation of Truncated α-Defensins, Current Protein & Peptide Science 2004; 5 (5) . https://dx.doi.org/10.2174/1389203043379459
DOI https://dx.doi.org/10.2174/1389203043379459 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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