Functional analysis of the a-defensin disulfide array in mouse cryptdin-4

Maemoto, A., Qu, Xiaoqing, Rosengren, K. J., Tanabe, H, Henschen-Edman, A., Craik, D. J. and Ouellette, A. J. (2004) Functional analysis of the a-defensin disulfide array in mouse cryptdin-4. The Journal of Biological Chemistry, 279 42: 44188-44196. doi:10.1074/jbc.M406154200

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ73495_OA.pdf Full text (open access) application/pdf 477.48KB 0

Author Maemoto, A.
Qu, Xiaoqing
Rosengren, K. J.
Tanabe, H
Henschen-Edman, A.
Craik, D. J.
Ouellette, A. J.
Title Functional analysis of the a-defensin disulfide array in mouse cryptdin-4
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2004
Sub-type Article (original research)
DOI 10.1074/jbc.M406154200
Open Access Status File (Publisher version)
Volume 279
Issue 42
Start page 44188
End page 44196
Total pages 9
Place of publication Bethesda
Publisher The American Soc for Biochemistry and Molecular Biology Inc
Collection year 2004
Language eng
Subject C1
250302 Biological and Medical Chemistry
780105 Biological sciences
Abstract The alpha-defensin antimicrobial peptide family is defined by a unique tridisulfide array. To test whether this invariant structural feature determines alpha-defensin bactericidal activity, mouse cryptdin-4 (Crp4) tertiary structure was disrupted by pairs of site-directed Ala for Cys substitutions. In a series of Crp4 disulfide variants whose cysteine connectivities were confirmed using NMR spectroscopy and mass spectrometry, mutagenesis did not induce loss of function. To the contrary, the in vitro bactericidal activities of several Crp4 disulfide variants were equivalent to or greater than those of native Crp4. Mouse Paneth cell alpha-defensins require the proteolytic activation of precursors by matrix metalloproteinase-7 (MMP-7), prompting an analysis of the relative sensitivities of native and mutant Crp4 and proCrp4 molecules to degradation by MMP-7. Although native Crp4 and the alpha-defensin moiety of proCrp4 resisted proteolysis completely, all disulfide variants were degraded extensively by MMP-7. Crp4 bactericidal activity was eliminated by MMP-7 cleavage. Thus, rather than determining alpha-defensin bactericidal activity, the Crp4 disulfide arrangement confers essential protection from degradation by this critical activating proteinase.
Keyword Biochemistry & Molecular Biology
Antibacterial Activities
Antimicrobial Peptides
Neutrophil Defensins
Q-Index Code C1

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 93 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 98 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 04:38:46 EST