NDLI: Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Barran, Perdita Mccullough, Bryan Campopiano, Dominic J. Seo, Emily Govan, John R. W. Oppenheim, Joost Dorin, Julia R. Chin, Wutharath Yang, De Uhrin, Dusan Macmillan, Derek Clarke, David J. Taylor, Karen
Description	Author Affiliation: Taylor K ( Medical Research Council Human Genetics Unit, Edinburgh EH4 2XU, Scotland, United Kingdom.)
Abstract	beta-Defensins are important in mammalian immunity displaying both antimicrobial and chemoattractant activities. Three canonical disulfide intramolecular bonds are believed to be dispensable for antimicrobial activity but essential for chemoattractant ability. However, here we show that HBD3 (human beta-defensin 3) alkylated with iodoactemide and devoid of any disulfide bonds is still a potent chemoattractant. Furthermore, when the canonical six cysteine residues are replaced with alanine, the peptide is no longer active as a chemoattractant. These findings are replicated by the murine ortholog Defb14. We restore the chemoattractant activity of Defb14 and HBD3 by introduction of a single cysteine in the fifth position (Cys V) of the beta-defensin six cysteine motif. In contrast, a peptide with a single cysteine at the first position (Cys I) is inactive. Moreover, a range of overlapping linear fragments of Defb14 do not act as chemoattractants, suggesting that the chemotactic activity of this peptide is not dependent solely on an epitope surrounding Cys V. Full-length peptides either with alkylated cysteine residues or with cysteine residues replaced with alanine are still strongly antimicrobial. Defb14 peptide fragments were also tested for antimicrobial activity, and peptides derived from the N-terminal region display potent antimicrobial activity. Thus, the chemoattractant and antimicrobial activities of beta-defensins can be separated, and both of these functions are independent of intramolecular disulfide bonds. These findings are important for further understanding of the mechanism of action of defensins and for therapeutic design.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	11
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-03-14
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anti-Infective Agents Pharmacology Biochemistry Chemotactic Factors Chemistry Beta-Defensins Metabolism Amino Acid Sequence Animals Cysteine Disulfides Magnetic Resonance Spectroscopy Mice Mice, Inbred C57BL Mice, Inbred DBA Molecular Sequence Data Tissue Distribution Research Support, Non-U.S. Gov't Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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