Biosynthesis of Defensins and Other Antimicrobial Peptides

  1. Joan Marsh Organizer and
  2. Jamie A. Goode
  1. Tomas Ganz

Published Online: 28 SEP 2007

DOI: 10.1002/9780470514658.ch4

Ciba Foundation Symposium 186 - Antimicrobial Peptides

Ciba Foundation Symposium 186 - Antimicrobial Peptides

How to Cite

Ganz, T. (2007) Biosynthesis of Defensins and Other Antimicrobial Peptides, in Ciba Foundation Symposium 186 - Antimicrobial Peptides (eds J. Marsh and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470514658.ch4

Author Information

  1. Department of Medicine, University of California at Los Angeles, Room 37–055, Center for the Health Sciences, Los Angeles, CA 90024, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471950257

Online ISBN: 9780470514658

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Keywords:

  • biosynthesis of defensins;
  • antimicrobial peptides;
  • subcellular transport;
  • polymorphonuclear leukocytes;
  • α2-macroglobulin

Summary

Defensins are small (about 30 amino acid residues) cationic antimicrobial peptides with a conserved framework of six disulphide-linked cysteines. Human defensin HNP-1 and the closely related HNP-3 are amphiphilic dimers that act in part by permeabilizing cell membranes. Defensin mRNAs, abundant in neutrophilic promyelocytes, certain non-human macrophages and Paneth cells, encode 94–100 amino acid prepropeptides. PreproHNP-1 is post-translationally processed to inactive proHNP-l then to mature HNP-I stored in granules. Bactenecin Bac-5 and perhaps other related neutrophil peptides are also synthesized as prepropeptides but are stored in granules as inactive propeptides. Their conserved cathelin-like propiece inhibits the cysteine protease, cathepsin L, and is removed only during granule release. Charge neutralization of mature peptide by the propiece is seen in both probactenecins and prodefensins. In contrast the propiece of cecropins is very short and procecropins are microbicidal. The pathways that convert myeloid preprodefensins to defensins are specific to myeloid cells but the signal for targeting to granules also functions in non-myeloid granulated cells. The truncation of the anionic propiece by deletion mutagenesis dramatically reduces defensin synthesis, suggesting that the propiece may assist in peptide stabilization, folding or subcellular transport. Despite some similarities in the mechanism of action of the various families of antimicrobial peptides, their precursors differ greatly, presumably owing to differing functions of the propieces.