Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function

Moroz, Olga V.; Burkitt, William; Wittkowski, Helmut; He, Wei; Ianoul, Anatoli; Novitskaya, Vera; Xie, Jingjing; Polyakova, Oxana; Lednev, Igor K.; Shekhtman, Alexander; Derrick, Peter J.; Bjoerk, Per; Foell, Dirk; Bronstein, Igor B.

doi:10.1186/1471-2091-10-11

Cited by 101 publications

(118 citation statements)

References 61 publications

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“…No binding of P290-310 was observed in the absence of calcium (data not shown). The increased affinity in the presence of Zn 2ϩ is consistent with a positive regulatory function of Zn 2ϩ on the Ca 2ϩ -dependent interaction of S100 with target proteins (19,38,39) The ATAD3A 290-310 peptide represents one of the highest-affinity small-peptide targets for S100B (54) ( Table 1).…”

Section: Resultsmentioning

confidence: 64%

The Calcium-Dependent Interaction between S100B and the Mitochondrial AAA ATPase ATAD3A and the Role of This Complex in the Cytoplasmic Processing of ATAD3A

Gilquin

Cannon

Hubstenberger

et al. 2010

Molecular and Cellular Biology

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S100 proteins comprise a multigene family of EF-hand calcium binding proteins that engage in multiple functions in response to cellular stress. In one case, the S100B protein has been implicated in oligodendrocyte progenitor cell (OPC) regeneration in response to demyelinating insult. In this example, we report that the mitochondrial ATAD3A protein is a major, high-affinity, and calcium-dependent S100B target protein in OPC. In OPC, ATAD3A is required for cell growth and differentiation. Molecular characterization of the S100B binding domain on ATAD3A by nuclear magnetic resonance (NMR) spectroscopy techniques defined a consensus calcium-dependent S100B binding motif. This S100B binding motif is conserved in several other S100B target proteins, including the p53 protein. Cellular studies using a truncated ATAD3A mutant that is deficient for mitochondrial import revealed that S100B prevents cytoplasmic ATAD3A mutant aggregation and restored its mitochondrial localization. With these results in mind, we propose that S100B could assist the newly synthesized ATAD3A protein, which harbors the consensus S100B binding domain for proper folding and subcellular localization. Such a function for S100B might also help to explain the rescue of nuclear translocation and activation of the temperature-sensitive p53val135 mutant by S100B at nonpermissive temperatures.

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Section: Resultsmentioning

confidence: 64%

The Calcium-Dependent Interaction between S100B and the Mitochondrial AAA ATPase ATAD3A and the Role of This Complex in the Cytoplasmic Processing of ATAD3A

Gilquin

Cannon

Hubstenberger

et al. 2010

Molecular and Cellular Biology

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“…S100A12 is an EF-hand calcium-binding protein that forms an antiparallel noncovalent homodimer (39) and binds calcium, zinc, and copper (14,39,(63)(64)(65). Like other secreted S100 proteins, S100A12 can form higher-order oligomers in the high calcium concentrations outside cells, including tetramers and hexamers (39).…”

Section: Discussionmentioning

confidence: 99%

“…*, P Ͻ 0.05 compared to medium alone (Student's t test). (39,65,66). S100 proteins have recently been recognized as important players in host metal sequestration strategies that contribute to nutritional immunity (18,20,22).…”

Section: Discussionmentioning

confidence: 99%

The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence

et al. 2015

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f During infectious processes, antimicrobial proteins are produced by both epithelial cells and innate immune cells. Some of these antimicrobial molecules function by targeting transition metals and sequestering these metals in a process referred to as "nutritional immunity." This chelation strategy ultimately starves invading pathogens, limiting their growth within the vertebrate host. Recent evidence suggests that these metal-binding antimicrobial molecules have the capacity to affect bacterial virulence, including toxin secretion systems. Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, or calgranulin A/B) binds zinc and represses the elaboration of the H. pylori cag type IV secretion system (T4SS). However, there are several other S100 proteins that are produced in response to infection. We hypothesized that the zinc-binding protein S100A12 (calgranulin C) is induced in response to H. pylori infection and also plays a role in controlling H. pylori growth and virulence. To test this, we analyzed gastric biopsy specimens from H. pylori-positive and -negative patients for S100A12 expression. These assays showed that S100A12 is induced in response to H. pylori infection and inhibits bacterial growth and viability in vitro by binding nutrient zinc. Furthermore, the data establish that the zinc-binding activity of the S100A12 protein represses the activity of the cag T4SS, as evidenced by the gastric cell "hummingbird" phenotype, interleukin 8 (IL-8) secretion, and CagA translocation assays. In addition, high-resolution field emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that S100A12 represses biogenesis of the cag T4SS. Together with our previous work, these data reveal that multiple S100 proteins can repress the elaboration of an oncogenic bacterial surface organelle. Helicobacter pylori is a Gram-negative member of the Epsilonproteobacteria commonly found in the human stomach (1). More than 50% of the world's population is chronically infected with H. pylori, despite a robust immune response to this bacterium (2, 3). The vast majority of infected persons exhibit no symptoms of disease; however, the presence of this pathogen can increase the risk of negative outcomes, including duodenal ulcer, dysplasia, mucosa-associated lymphoid tissue (MALT) lymphoma, and invasive gastric cancer (4). Negative outcomes of H. pylori infection are associated with multiple factors, including host genetics, environmental contributions such as diet and smoking, and bacterial virulence properties.One major virulence factor that contributes to H. pylori-associated disease outcomes is the cag pathogenicity island-encoded type IV secretion system (cag T4SS) (5). The cag T4SS is a macromolecular nanomachine responsible for translocating substrates, including peptidoglycan and the oncogenic effector molecule CagA, into host epithelial cells (6). The translocation activity of the cag T4SS leads to multiple consequences in host cell biology, including cytoskeletal rearrangements, indu...

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“…77 Affinity of S100A12 for the V domain of RAGE increases >1,000-fold in the Ca 2+ -78 or Zn 2+ -bound hexameric states. 79 Only S100A9 with Ca 2+ and Zn 2+ has high affinity for RAGE; S100A8 has virtually none, and S100A8/A9 binding is relatively weak. 80 Additional putative receptors include N-glycans (glycosylated RAGE) and carboxylated N-glycans, a G-protein-coupled receptor, scavenger receptors (reviewed in Goyette & Geczy 64 ).…”

Section: Extracellular Functions and Receptors Of Calgranulinsmentioning

confidence: 99%

Calgranulins May Contribute Vascular Protection In Atherogenesis

Geczy

Chung

Hiroshima

2014

Circ J

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Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function

Cited by 101 publications

References 61 publications

The Calcium-Dependent Interaction between S100B and the Mitochondrial AAA ATPase ATAD3A and the Role of This Complex in the Cytoplasmic Processing of ATAD3A

The Calcium-Dependent Interaction between S100B and the Mitochondrial AAA ATPase ATAD3A and the Role of This Complex in the Cytoplasmic Processing of ATAD3A

The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence

Calgranulins May Contribute Vascular Protection In Atherogenesis

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