Magnetic circular dichroism studies of iron(<scp>ii</scp>) binding to human calprotectin

Baker, Tessa M.; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Neidig, Michael L.

doi:10.1039/c6sc03487j

Cited by 22 publications

(46 citation statements)

References 32 publications

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“…Moreover, the exclusion of a solvent-derived ligand at site 1 in the presence of Ca(II) is reminiscent of our prior work on the His 6 site, which supports a model in which the S100A9 C-terminal tail precludes access of water molecules to the metal center and thereby contributes to the metal-sequestering function of CP. 12,15 …”

Section: Discussionmentioning

confidence: 99%

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His₃Asp Site

et al. 2018

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Calprotectin (CP, S100A8/S100A9 oligomer, MRP-8/MRP-14 oligomer) is a host-defense protein that sequesters nutrient transition metals from microbes. Each S100A8/S100A9 heterodimer contains four EF-hand domains and two transition-metal-binding sites. We investigate the effect of Ca(II) ions on the structure and Ni(II)-binding properties of human CP. By employing energy dispersive X-ray (EDX) spectroscopy, we evaluate the metal content of Ni(II)-bound CP-Ser (oligomer of S100A8(C42S) and S100A9(C3S)) crystals obtained in the absence and presence of Ca(II). We present a 2.1-Å resolution crystal structure of Ni(II)-bound CP-Ser and compare this structure to a reported Ni(II)- and Ca(II)-bound CP-Ser structure (Nakashige, T. G. et al. J. Am. Chem. Soc. 2017, 139, 8828–8836). This analysis reveals conformational changes associated with Ca(II) coordination to the EF-hands of S100A9, and that Ca(II) binding affects the coordination number and geometry of the Ni(II) ion bound to the His3Asp site. In contrast, negligible differences are observed for the Ni(II)-His6 site in the absence and presence of Ca(II). Biochemical studies show that, whereas the His6 site has a thermodynamic preference for Ni(II) over Zn(II), the His3Asp site selects for Zn(II) over Ni(II), and relatively rapid metal exchange occurs at this site. These observations inform the working model for how CP withholds nutrient metals in the extracellular space.

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Section: Discussionmentioning

confidence: 99%

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His₃Asp Site

et al. 2018

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“…apparent K d,Fe(II) < 2.2 pM, +Ca). 24 Although site 1 also chelates Fe(II), 48 the affinity of this site for Fe(II) is relatively low, and our prior work indicates that only site 2 contributes to Fe(II) withholding. 24 …”

Section: Introductionmentioning

confidence: 99%

Human calprotectin affects the redox speciation of iron

Nakashige

Nolan

2017

Metallomics

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We report that the metal-sequestering human host-defense protein calprotectin (CP, S100A8/S100A9 oligomer) affects the redox speciation of iron (Fe) in bacterial growth media and buffered aqueous solution. Under aerobic conditions and in the absence of an exogenous reducing agent, CP-Ser (S100A8(C42S)/S100A9(C3S) oligomer) depletes Fe from three different bacterial growth media preparations over a 48-h timeframe (T = 30 °C). The presence of the reducing agent β-mercaptoethanol accelerates this process and allows CP-Ser to deplete Fe over a ≈1-h timeframe. Fe-depletion assays performed with metal-binding-site variants of CP-Ser show that the hexahistidine (His6) site, which coordinates Fe(II) with high affinity, is required for Fe depletion. An analysis of Fe redox speciation in buffer containing Fe(III) citrate performed under aerobic conditions demonstrates that CP-Ser causes a time-dependent increase in the [Fe(II)]/[Fe(III)] ratio. Taken together, these results indicate that the hexahistidine site of CP stabilizes Fe(II) and thereby shifts the redox equilibrium of Fe to the reduced ferrous state under aerobic conditions. We also report that the presence of bacterial metabolites affects the Fe-depleting activity of CP-Ser. Supplementation of bacterial growth media with an Fe(III)-scavenging siderophore (enterobactin, staphyloferrin B, or desferrioxamine B) attenuates the Fe-depleting activity of CP-Ser. This result indicates that formation of Fe(III)-siderophore complexes blocks CP-mediated reduction of Fe(III) and hence the ability of CP to coordinate Fe(II). In contrast, the presence of pyocyanin (PYO), a redox-cycling phenazine produced by Pseudomonas aeruginosa that reduces Fe(III) to Fe(II), accelerates Fe depletion by CP-Ser under aerobic conditions. These findings indicate that the presence of microbial metabolites that contribute to metal homeostasis at the host/pathogen interface can affect the metal-sequestering function of CP.

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“…CP is the heterodimer of S100A8 and S100A9 (Hunter and Chazin, 1998). Two transition metal binding sites are formed at the dimer interface of CP that bind Zn and other nutrient metals (Baker et al, 2017;Corbin et al, 2008;Damo et al, 2013;Kehl-Fie et al, 2011;Nakashige et al, 2017). CP inhibits bacterial growth in vitro, and this inhibition is dependent on the metal-binding properties of the protein (Corbin et al, 2008;Hood et al, 2012;Kehl-Fie et al, 2011;Zackular et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

An Acinetobacter baumannii, Zinc-Regulated Peptidase Maintains Cell Wall Integrity during Immune-Mediated Nutrient Sequestration

et al. 2019

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Magnetic circular dichroism studies of iron(ii) binding to human calprotectin

Abstract: Magnetic circular dichroism studies of Fe(ii) binding to human calprotectin demonstrate the nature of Fe(ii) coordination at two different Fe(ii)-binding sites and provide insight into how Ca(ii) modulates Fe(ii) coordination.

Cited by 22 publications

References 32 publications

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His₃Asp Site

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His₃Asp Site

Human calprotectin affects the redox speciation of iron

An Acinetobacter baumannii, Zinc-Regulated Peptidase Maintains Cell Wall Integrity during Immune-Mediated Nutrient Sequestration

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Magnetic circular dichroism studies of iron(ii) binding to human calprotectin

Abstract: Magnetic circular dichroism studies of Fe(ii) binding to human calprotectin demonstrate the nature of Fe(ii) coordination at two different Fe(ii)-binding sites and provide insight into how Ca(ii) modulates Fe(ii) coordination.

Cited by 22 publications

References 32 publications

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His3Asp Site

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His3Asp Site

Human calprotectin affects the redox speciation of iron

An Acinetobacter baumannii, Zinc-Regulated Peptidase Maintains Cell Wall Integrity during Immune-Mediated Nutrient Sequestration

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Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His₃Asp Site

Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His₃Asp Site