Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide
Name
HD5Zn-ACSCB-RevisedFinalMS-062213.pdf
Description
article
Size
14.19 MB
Format
Adobe PDF
Checksum (MD5)
7ff51cbc22055a8346a4ff89eb4d2cf6
Author(s)
Zhang, Yunfei
Cougnon, Fabien
Wanniarachchi, Yoshitha A.
Hayden, Joshua A.
Nolan, Elizabeth M.
Date Issued
July 2013
Journal
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Citation
Zhang, Yunfei, Fabien Cougnon, Yoshitha A. Wanniarachchi, Joshua A. Hayden, and Elizabeth M. Nolan. "Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide." ACS Chem. Biol., 2013, 8 (9), pp 1907–1911
Version
Author's final manuscript
Abstract
Human defensin 5 (HD5) is a 32-residue cysteine-rich host-defense peptide that exhibits three disulfide bonds in the oxidized form (HD5[subscript ox]). It is abundant in small intestinal Paneth cells, which release HD5 into the intestinal lumen and house a labile Zn(II) store of unknown function. Here, we consider the redox properties of HD5 and report that the reduced form, HD5[subscript red], is a metal-ion chelator. HD5 has a midpoint potential of −257 mV at pH 7.0. HD5[subscript red] utilizes its cysteine residues to coordinate one equivalent of Zn(II) with an apparent K[subscript d1] value in the midpicomolar range. Zn(II) or Cd(II) binding perturbs the oxidative folding pathway of HD5[subscript red] to HD5[subscript ox]. Whereas HD5[subscript red] is highly susceptible to proteolytic degradation, the Zn(II)-bound form displays resistance to hydrolytic breakdown by trypsin and other proteases. The ability of a reduced defensin peptide to coordinate Zn(II) provides a putative mechanism for how these peptides persist in vivo.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/cb400340k
