Structural Analysis of S100A8 Complex with Zinc and Calcium: A General Protocol for the Study of S100 Proteins in the Presence of Divalent Cations by X-Ray Crystallography

Yatime, Laure

doi:10.1007/978-1-4939-9030-6_26

Cited by 4 publications

(2 citation statements)

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“…Цинк-связывающий сайт в белках S100B, S100A6, S100A7, S100A8/A9, S100A12 и S100A15 состоит из трёх остатков гистидина и одного остатка аспартата либо четырёх остатков гистидина; а S100A2, S100A3 и S100A4 имеют цистеин-содержащие цинк-связывающие сайты [94]. Роль такого связывания до конца не изучена, однако предполагают, что двухвалентные катионы, не только кальций, но и цинк, медь и марганец, влияют на олигомеризацию бел-ков S100, следовательно, и на их функциональную способность [96,97] 10. Другие комплексообразующие соеди нения.…”

Section: металломика цинкаunclassified

Metal-ligand forms of iron and zinc in the human body

et al. 2022

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Metals have a wide range of effects on biological processes, playing an important role in maintaining the functioning of the human body. However, many metals, including essential elements, can have a toxic effect on the body, leading to pathological processes. The biological role of an element depends on a number of physicochemical facts, such as the oxidation degree and the formation of metal-ligand organic and inorganic complexes. For example, most of the iron binds to transferrin and ferritin ensuring the safe transportation of the fenton-active trivalent metal ions in the bloodstream. Free Fe3+ ions lead to the formation of reactive oxygen species and further damage of cell structures. Thus, the chemical form of the element determines the toxicokinetics and toxicodynamics of metals. Knowledge in total exposure of elements in biological fluids is not enough to understand the complex mechanism of biological and abnormal reactions. It is necessary to study the interaction of metal elements with various ligands such as high- and low-molecular compounds (proteins, polysaccharides, nucleic acids, citrates, amino acids). In this regard, the application of modern analytical methods is becoming increasingly important to obtain qualitative and quantitative data on elements, ionic forms, speciation and functions in biological systems. The combination of these methods is called speciation analysis, which is a well-established way to study the biological role and metabolism of trace elements. This article reviews the main metal-ligand forms of iron (transferrin, albumin, ferritin and citrate) and zinc (albumin, 2-macroglobulin, IgG, transcuprein, metallothioneins, ZIP and ZnT transporters). This information can be useful both in fundamental and applied researches in the biology and medicine.

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Section: металломика цинкаunclassified

Metal-ligand forms of iron and zinc in the human body

et al. 2022

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“…The resulting mS100A9:pETM11 constructs were used to transform E. coli BL21 (DE3) cells. Protein expression and purification was carried out as described previously (Yatime, 2019). Transformed cells were grown at 37ºC for 4 hours and protein expression was induced overnight at 18ºC by adding 1 mM IPTG in the culture medium.…”

Section: Expression and Purification Of Ms100a9 Wt And Mutant Proteinsmentioning

confidence: 99%

Divalent cations influence the dimerization mode of murine S100A9 protein by modulating its disulfide bond pattern

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Paris

Mas

et al. 2021

Journal of Structural Biology

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The crystallographic structure of mS100A9 bound to calcium and zinc is reported A novel Zn-binding site and a disulfide bridge rigidify mS100A9 C-terminus In solution, mS100A9 exists both as non-covalent and disulfide-crosslinked homodimers Divalent cations modulate the relative proportion of the different mS100A9 homodimers 2 Abstract S100A9, with its congener S100A8, belongs to the S100 family of calcium-binding proteins found exclusively in vertebrates. These two proteins are major constituents of neutrophils. In response to a pathological condition, they can be released extracellularly and become alarmins that induce both pro-and anti-inflammatory signals, through specific cell surface receptors. They also act as antimicrobial agents, mainly as a S100A8/A9 heterocomplex, through metal sequestration. The mechanisms whereby divalent cations modulate the extracellular functions of S100A8 and S100A9 are still unclear. Importantly, it has been proposed that these ions may affect both the ternary and quaternary structure of these proteins, thereby influencing their physiological properties. In the present study, we report the crystal structures of WT and C80A murine S100A9 (mS100A9), determined at 1.45 and 2.35 Å resolution, respectively, in the presence of calcium and zinc. These structures reveal a canonical homodimeric form for the protein. They also unravel an intramolecular disulfide bridge that stabilizes the C-terminal tail in a rigid conformation, thus shaping a second Zn-binding site per S100A9 protomer. In solution, mS100A9 apparently binds only two zinc ions per homodimer, with an affinity in the micromolar range, and aggregates in the presence of excess zinc. Using mass spectrometry, we demonstrate that mS100A9 can form both non-covalent and covalent homodimers with distinct disulfide bond patterns. Interestingly, calcium and zinc seem to affect differentially the relative proportion of these forms. We discuss how the metal-dependent interconversion between mS100A9 homodimers may explain the versatility of physiological functions attributed to the protein.

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