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dc.contributor.authorFonner, Brittany A.
dc.contributor.authorTripet, Brian P.
dc.contributor.authorEilers, Brian J.
dc.contributor.authorStanisich, Jessica J.
dc.contributor.authorSullivan-Springhetti, Rose K.
dc.contributor.authorMoore, Rebecca
dc.contributor.authorLiu, Mengyao
dc.contributor.authorLei, Benfang
dc.contributor.authorCopié, Valérie
dc.date.accessioned2016-01-27T18:31:09Z
dc.date.available2016-01-27T18:31:09Z
dc.date.issued2014-06
dc.identifier.citationFonner, Brittany A., Brian P. Tripet, Brian J. Eilers, Jessica Stanisich, Rose K. Sullivan-Springhetti, Rebecca Moore, Mengyao Liu, Benfang Lei, and Valérie Copié. “ Solution Structure and Molecular Determinants of Hemoglobin Binding of the First NEAT Domain of IsdB in Staphylococcus Aureus .” Biochemistry 53, no. 24 (June 24, 2014): 3922–3933. doi:10.1021/bi5005188.en_US
dc.identifier.issn0006-2960
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/9522
dc.description.abstractThe human pathogen Staphylococcus aureus acquires heme iron from hemoglobin (Hb) via the action of a series of iron-regulated surface determinant (Isd) proteins. The cell wall anchored IsdB protein is recognized as the predominant Hb receptor, and is comprised of two NEAr transporter (NEAT) domains that act in concert to bind, extract, and transfer heme from Hb to downstream Isd proteins. Structural details of the NEAT 2 domain of IsdB have been investigated, but the molecular coordination between NEAT 2 and NEAT 1 to extract heme from hemoglobin has yet to be characterized. To obtain a more complete understanding of IsdB structure and function, we have solved the 3D solution structure of the NEAT 1 domain of IsdB (IsdBN1) spanning residues 125–272 of the full-length protein by NMR. The structure reveals a canonical NEAT domain fold and has particular structural similarity to the NEAT 1 and NEAT 2 domains of IsdH, which also interact with Hb. IsdBN1 is also comprised of a short N-terminal helix, which has not been previously observed in other NEAT domain structures. Interestingly, the Hb binding region (loop 2 of IsdBN1) is disordered in solution. Analysis of Hb binding demonstrates that IsdBN1 can bind metHb weakly and the affinity of this interaction is further increased by the presence of IsdB linker domain. IsdBN1 loop 2 variants reveal that phenylalanine 164 (F164) of IsdB is necessary for Hb binding and rapid heme transfer from metHb to IsdB. Together, these findings provide a structural role for IsdBN1 in enhancing the rate of extraction of metHb heme by the IsdB NEAT 2 domain.en_US
dc.description.sponsorshipThe NMR experiments were recorded at Montana State University on a DRX600 Bruker solution NMR spectrometer, purchased in part with funds from the NIH Shared Instrumentation Grant (SIG) (Grant Number 1S10-RR13878-01), and recently upgraded to an AVANCE III console and cryogenically cooled TCI probe (Grant Number 1S10-RR026659-01). We thank the Research Experience for Undergraduates (REU) program from the Department of Chemistry and Biochemistry (funded through NSF Grant 1156855) for support of REU undergraduate student R.M., and MSU’s Emerging Scholar program for support of under-graduate student R.K.S.-S.en_US
dc.titleSolution Structure and Molecular Determinants of Hemoglobin Binding of the first NEAT Domain of IsdB in Staphylococcus aureusen_US
dc.typeArticleen_US
mus.citation.extentfirstpage3922en_US
mus.citation.extentlastpage3933en_US
mus.citation.issue24en_US
mus.citation.journaltitleBiochemistryen_US
mus.citation.volume53en_US
mus.identifier.categoryHealth & Medical Sciencesen_US
mus.identifier.doi10.1021/bi5005188en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US


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