His-X-X-X-His motif in S100 protein, calprotectin: relation to microbiostatic activity

Clohessy, Paul A.; Golden, Barbara E.

doi:10.1002/jlb.60.5.674

Cited by 19 publications

(16 citation statements)

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“…A high-affinity Zn 2ϩ binding site has been proposed in each of the two S100 chains (45). Several reports suggest that S100A8/A9 inhibits bacterial and fungal growth by zinc chelation and depletion of zinc, a necessary component of microbial growth (20, 24, 25, 46 -48).…”

Section: Discussionmentioning

confidence: 99%

“…Protonation of histidine requires a pH below 6, the pKa value of the histidine side group. Both S100A8 and A9 have histidine-rich regions (45,47), and a possible explanation for the pH dependence of the bactericidal effect may be that it is dependent on a positive charge of the histidine-rich regions of one or both of the subunits. No killing of the bacteria by S100A8/A9 was seen at pH 7.5.…”

Section: Discussionmentioning

confidence: 99%

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Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Åkerström

Björck

2009

The Journal of Immunology

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Finegoldia magna is an anaerobic bacterial species that is part of the normal human flora on all nonsterile body surfaces, but it is also a significant opportunistic pathogen causing a wide range of infections. Some isolates of F. magna that are more frequently associated with clinical infection express protein L, a surface protein containing multiple homologous domains (B1-B5) that bind Igs through interactions with Ig L chains. The present study shows that the N-terminal A domain of protein L binds S100A8/A9, antibacterial proteins present in large amounts in the cytoplasm of neutrophils, but also extracellularly in tissues during inflammation. As a result, protein L-expressing F. magna are protected against killing by S100A8/A9. Igs and S100A8/A9 were found to interact independently with protein L, demonstrating that this bacterial surface protein is capable of manipulating both adaptive and innate immune defense mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Åkerström

Björck

2009

The Journal of Immunology

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“…In addition to the binding to Ca 2ϩ , S100A8/A9 has been shown to bind other bivalent cations, such as Zn 2ϩ and Cu 2ϩ [4, 16 -19]. The binding motif for these bivalent cations is still in debate [17,18,20]. It is interesting that one putative zincbinding site has been associated with the specific binding of polyunsaturated fatty acids, another feature of S100A8/A9 [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions

Ghavami

Kerkhoff

Łos

et al. 2004

Journal of Leukocyte Biology

135

112

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The protein complex S100A8/A9, abundant in the cytosol of neutrophils, is secreted from the cells upon cellular activation and induces apoptosis in tumor cell lines and normal fibroblasts in a zinc-reversible manner. In the present study, we present evidence that the S100A8/A9 also exerts its apoptotic effect by a zinc-independent mechanism. Treatment of the colon carcinoma cells with different concentrations of human S100A8/A9 or the metal ion chelator diethylenetriaminepentacetic acid (DTPA) resulted in a significant increase of cell death. Annexin V/phosphatidylinositol and Hoechst 33258 staining revealed that cell death was mainly of the apoptotic type. A significant increase in the activity of caspase-3 and -9 was observed in both cell lines after treatment. Caspase-8 activation was negligible in both cell lines. The cytotoxicity/apoptotic effect of human S100A8/A9 and DTPA was inhibited significantly (P<0.05) by Zn ؉2 and Cu ؉2, more effectively than by Ca 2؉ and Mg 2؉. The antioxidant N-acetyl-Lcysteine inhibited the cytotoxicity/apoptotic effect of S100A8/A9 and DTPA. However, as a result of the different time-courses of both agents and that the S100A8/A9-induced apoptosis was not completely reversed, we conclude that S100A8/A9 exerts its apoptotic effect on two colon carcinoma cell lines through a dual mechanism: one via zinc exclusion from the target cells and the other through a yet-undefined mechanism, probably relaying on the cell-surface receptor(s). J. Leukoc. Biol. 76: 169 -175; 2004.

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“…In addition, S100A9 C-terminal residues 103-105 form a polyhistidine motif (HHH), which may be involved in zinc binding (26,27). Also suggested to be zinc-binding domains, the HXXXH motifs in S100A8 and S100A9 are commonly found in S100 proteins (4,27,28). Because zinc is required for bacterial growth, either the polyhistidine or HXXXH motifs have been suggested to bind and sequester zinc from microorganisms and inhibit bacterial growth (4,(27)(28)(29).…”

mentioning

confidence: 99%

“…Also suggested to be zinc-binding domains, the HXXXH motifs in S100A8 and S100A9 are commonly found in S100 proteins (4,27,28). Because zinc is required for bacterial growth, either the polyhistidine or HXXXH motifs have been suggested to bind and sequester zinc from microorganisms and inhibit bacterial growth (4,(27)(28)(29). In addition to zinc, calprotectin chelates other metal ions, including Mn 2ϩ , which inhibits growth of S. aureus in tissue abscesses (30).…”

mentioning

confidence: 99%

Calprotectin S100A9 Calcium-binding Loops I and II Are Essential for Keratinocyte Resistance to Bacterial Invasion

Champaiboon

Sappington

Guenther

et al. 2009

Journal of Biological Chemistry

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Epithelial cells expressing calprotectin, a heterodimer of S100A8 and S100A9 proteins, are more resistant to bacterial invasion. To determine structural motifs that affect resistance to bacterial invasion, mutations were constructed in S100A9 targeting the calcium-binding loops I and II (E36Q, E78Q, E36Q,E78Q) and the C terminus (S100A9 1-99 and S100A9 1-112 ), which contains putative antimicrobial zinc-binding and phosphorylation sites. The S100A8 and mutated S100A9 encoding plasmids were transfected into calprotectin-negative KB carcinoma cells. All transfected cells (except KB-sham) expressed 27E10-reactive heterodimers. In bacterial invasion assays with Listeria monocytogenes and Salmonella enterica serovar Typhimurium (Salmonella typhimurium), cell lines expressing S100A8 in complex with S100A9 E36Q , S100A9 E78Q , S100A9 1-99 , or S100A9 1-112 mutants or the S100A9 1-114 (full-length) calprotectin resisted bacterial invasion better than KB-sham. When compared with KB-S100A8/A9 1-114 , cells expressing truncated S100A9 1-99 or S100A9 1-112 with S100A8 also showed increased resistance to bacterial invasion. In contrast, glutamic acid residues 36 and 78 in calcium-binding loops I and II promote resistance in epithelial cells, because cells expressing S100A9 E36Q,E78Q with S100A8 were unable to resist bacterial invasion. Mutations in S100A9 E36Q, E78Q were predicted to cause loss of the calcium-induced positive face in calprotectin, reducing interactions with microtubules and appearing to be crucial for keratinocyte resistance to bacterial invasion.

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His-X-X-X-His motif in S100 protein, calprotectin: relation to microbiostatic activity

Cited by 19 publications

References 0 publications

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions

Calprotectin S100A9 Calcium-binding Loops I and II Are Essential for Keratinocyte Resistance to Bacterial Invasion

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