Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide
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. He...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/88524 https://orcid.org/0000-0002-6153-8803 https://orcid.org/0000-0002-6426-2291 |
| _version_ | 1811075870357454848 |
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| author | Zhang, Yunfei Cougnon, Fabien Wanniarachchi, Yoshitha A. Hayden, Joshua A. Nolan, Elizabeth M. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Zhang, Yunfei Cougnon, Fabien Wanniarachchi, Yoshitha A. Hayden, Joshua A. Nolan, Elizabeth M. |
| author_sort | Zhang, Yunfei |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:13:06Z |
| format | Article |
| id | mit-1721.1/88524 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:13:06Z |
| publishDate | 2014 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/885242022-09-26T16:28:59Z Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide Zhang, Yunfei Cougnon, Fabien Wanniarachchi, Yoshitha A. Hayden, Joshua A. Nolan, Elizabeth M. Massachusetts Institute of Technology. Department of Chemistry Nolan, Elizabeth M. Zhang, Yunfei Cougnon, Fabien Wanniarachchi, Yoshitha A. Hayden, Joshua A. Nolan, Elizabeth M. 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. National Institutes of Health (U.S.) (Grant DP2OD007045) Kinship Foundation. Searle Scholars Program Massachusetts Institute of Technology. Dept. of Chemistry 2014-07-30T13:39:30Z 2014-07-30T13:39:30Z 2013-07 2013-05 Article http://purl.org/eprint/type/JournalArticle 1554-8929 1554-8937 http://hdl.handle.net/1721.1/88524 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 https://orcid.org/0000-0002-6153-8803 https://orcid.org/0000-0002-6426-2291 en_US http://dx.doi.org/10.1021/cb400340k ACS Chemical Biology 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. application/pdf American Chemical Society (ACS) Prof. Nolan via Erja Kajosalo |
| spellingShingle | Zhang, Yunfei Cougnon, Fabien Wanniarachchi, Yoshitha A. Hayden, Joshua A. Nolan, Elizabeth M. Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide |
| title | Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide |
| title_full | Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide |
| title_fullStr | Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide |
| title_full_unstemmed | Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide |
| title_short | Reduction of Human Defensin 5 Affords a High-Affinity Zinc-Chelating Peptide |
| title_sort | reduction of human defensin 5 affords a high affinity zinc chelating peptide |
| url | http://hdl.handle.net/1721.1/88524 https://orcid.org/0000-0002-6153-8803 https://orcid.org/0000-0002-6426-2291 |
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