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dc.contributor.authorHadley, Rose Currier
dc.contributor.authorGu, Yu
dc.contributor.authorNolan, Elizabeth Marie
dc.date.accessioned2020-06-01T16:41:44Z
dc.date.available2020-06-01T16:41:44Z
dc.date.issued2018-05
dc.identifier.issn0006-2960
dc.identifier.urihttps://hdl.handle.net/1721.1/125595
dc.description.abstractCalprotectin (CP) is an abundant host-defense protein that contributes to the metal-withholding innate immune response by sequestering nutrient metal ions from microbial pathogens in the extracellular space. Over the past decade, murine models of infectious disease have advanced understanding of the physiological functions of CP and its ability to compete with microbes for essential metal nutrients. Despite this extensive work, murine CP (mCP) has not been biochemically evaluated, and structural and biophysical understanding of CP is currently limited to the human orthologue. We present the reconstitution, purification, and characterization of mCP as well as the cysteine-null variant mCP-Ser. Apo mCP is a mS100A8/mS100A9 heterodimer, and Ca(II) binding causes two heterodimers to self-associate and form a heterotetramer. Initial metal-depletion studies demonstrate that mCP depletes multiple first-row transition metal ions, including Mn, Fe, Ni, Cu, and Zn, from complex microbial growth medium, indicating that mCP binds multiple nutrient metals with high affinity. Moreover, antibacterial activity assays show that mCP inhibits the growth of a variety of bacterial species. The metal-depletion and antibacterial activity studies also provide evidence that Ca(II) ions enhance these functional properties of mCP. This contribution provides the groundwork for understanding the similarities and differences between the human and murine orthologues of CP and for further elucidation of its biological coordination chemistry.en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Grant CHE-1352132)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01GM118695)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant P30-ES00210)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Grant 0070319)en_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases (U.S.) (Contract HHSN272200700055C)en_US
dc.language.isoen
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttps://dx.doi.org/10.1021/ACS.BIOCHEM.8B00309en_US
dc.rightsArticle 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.sourcePMCen_US
dc.titleInitial Biochemical and Functional Evaluation of Murine Calprotectin Reveals Ca(II)-Dependence and Its Ability to Chelate Multiple Nutrient Transition Metal Ionsen_US
dc.typeArticleen_US
dc.identifier.citationHadley, Rose C. , Yu Gu, and Elizabeth M. Nolan. “Initial Biochemical and Functional Evaluation of Murine Calprotectin Reveals Ca(II)-Dependence and Its Ability to Chelate Multiple Nutrient Transition Metal Ions.” Biochemistry 57 (2018): 2846-2856 © 2018 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.relation.journalBiochemistryen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-01-02T17:20:20Z
dspace.date.submission2020-01-02T17:20:23Z
mit.journal.volume57en_US
mit.journal.issue19en_US
mit.metadata.statusComplete


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