dc.contributor.author | Nakashige, Toshiki George | |
dc.contributor.author | Zygiel, Emily Mikayla | |
dc.contributor.author | Drennan, Catherine L | |
dc.contributor.author | Nolan, Elizabeth Marie | |
dc.date.accessioned | 2018-08-01T17:36:55Z | |
dc.date.available | 2018-08-01T17:36:55Z | |
dc.date.issued | 2017-07 | |
dc.date.submitted | 2017-02 | |
dc.identifier.issn | 0002-7863 | |
dc.identifier.issn | 1520-5126 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/117267 | |
dc.description.abstract | The human innate immune protein calprotectin (CP, S100A8/S100A9 oligomer, calgranulin A/calgranulin B oligomer, MRP-8/MRP-14 oligomer) chelates a number of first-row transition metals, including Mn(II), Fe(II), and Zn(II), and can withhold these essential nutrients from microbes. Here we elucidate the Ni(II) coordination chemistry of human CP. We present a 2.6-Å crystal structure of Ni(II)- and Ca(II)-bound CP, which reveals that CP binds Ni(II) ions at both its transition-metal-binding sites: the His3Asp motif (site 1) and the His6motif (site 2). Further biochemical studies establish that coordination of Ni(II) at the hexahistidine site is thermodynamically preferred over Zn(II). We also demonstrate that CP can sequester Ni(II) from two human pathogens, Staphylococcus aureus and Klebsiella pneumoniae, that utilize this metal nutrient during infection, and inhibit the activity of the Ni(II)-dependent enzyme urease in bacterial cultures. In total, our findings expand the biological coordination chemistry of Ni(II)-chelating proteins in nature and provide a foundation for evaluating putative roles of CP in Ni(II) homeostasis at the host-microbe interface and beyond. | en_US |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1021/JACS.7B01212 | en_US |
dc.rights | 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. | en_US |
dc.source | PMC | en_US |
dc.title | Nickel Sequestration by the Host-Defense Protein Human Calprotectin | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Nakashige, Toshiki G. et al. “Nickel Sequestration by the Host-Defense Protein Human Calprotectin.” Journal of the American Chemical Society 139, 26 (June 2017): 8828–8836 © 2017 American Chemical Society | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.mitauthor | Nakashige, Toshiki George | |
dc.contributor.mitauthor | Zygiel, Emily Mikayla | |
dc.contributor.mitauthor | Drennan, Catherine L | |
dc.contributor.mitauthor | Nolan, Elizabeth Marie | |
dc.relation.journal | Journal of the American Chemical Society | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-08-01T14:53:42Z | |
dspace.orderedauthors | Nakashige, Toshiki G.; Zygiel, Emily M.; Drennan, Catherine L.; Nolan, Elizabeth M. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-6234-8155 | |
dc.identifier.orcid | https://orcid.org/0000-0001-5486-2755 | |
dc.identifier.orcid | https://orcid.org/0000-0002-6153-8803 | |
mit.license | PUBLISHER_POLICY | en_US |