title: Reduction of human defensin 5 affords a high-affinity zinc-chelating peptide.
abstract: Human defensin 5 (HD5) is a 32-residue cysteine-rich host-defense peptide that exhibits three disulfide bonds in the oxidized form (HD5ox). 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, HD5red, is a metal-ion chelator. HD5 has a midpoint potential of -257 mV at pH 7.0. HD5red utilizes its cysteine residues to coordinate one equivalent of Zn(II) with an apparent Kd1 value in the midpicomolar range. Zn(II) or Cd(II) binding perturbs the oxidative folding pathway of HD5red to HD5ox. Whereas HD5red 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fabien B L
authors.initials: FB
authors.lastname: Cougnon
authors.forename: Yoshitha A
authors.initials: YA
authors.lastname: Wanniarachchi
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hayden
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Nolan
mesh_terms: D000595:Amino Acid Sequence; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D015032:Zinc / Q000378:metabolism*; D023084:alpha-Defensins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; C500225:DEFA5 protein, human; D023084:alpha-Defensins; D015032:Zinc