The C-Terminus and Linker Region of S100B Exert Dual Control on Protein−Protein Interactions with TRTK-12

McClintock, Kimberly A.; Eldik, Linda J. Van; Shaw, Gary S.

doi:10.1021/bi011732m

Cited by 26 publications

(41 citation statements)

References 44 publications

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“…This is consistent with the S100B calcium-dependent target recognition mechanism, because the interaction is inhibited by the well characterized target peptide TRTK-12. This peptide, which has the highest affinity for S100B of any known target (76), contains a consensus motif for S100B-binding that is conserved in several mammalian cytoskeletal proteins including tubulin, glial fibrillary acidic protein, and vimentin (13). Further, S100B and S100B-EGFP both produce the filamenting phenotype and show similar co-localization patterns, indicating that the EGFP fusion does not interfere with the target-binding regions in S100B located at its C terminus (helix IV) and linker (76).…”

Section: Discussionmentioning

confidence: 99%

“…This peptide, which has the highest affinity for S100B of any known target (76), contains a consensus motif for S100B-binding that is conserved in several mammalian cytoskeletal proteins including tubulin, glial fibrillary acidic protein, and vimentin (13). Further, S100B and S100B-EGFP both produce the filamenting phenotype and show similar co-localization patterns, indicating that the EGFP fusion does not interfere with the target-binding regions in S100B located at its C terminus (helix IV) and linker (76). Sedimentation equilibrium studies have shown that the EGFP moiety neither interferes with S100B dimerization nor causes oligomerization or aggregation of S100B-EGFP.…”

Section: Discussionmentioning

confidence: 99%

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Human S100B Protein Interacts with the Escherichia coli Division Protein FtsZ in a Calcium-sensitive Manner

Ferguson

Shaw

2004

Journal of Biological Chemistry

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S100B is a small, dimeric EF-hand calcium-binding protein abundant in vertebrates. Upon calcium binding, S100B undergoes a conformational change allowing it to interact with a variety of target proteins, including the cytoskeletal proteins tubulin and glial fibrillary acidic protein. In both cases, S100B promotes the in vitro disassembly of these proteins in a calcium-sensitive manner. Despite this, there is little in vivo evidence for the interaction of proteins such as tubulin with S100B. To probe these interactions, we studied the expression of human S100B in Escherichia coli and its interaction with the prokaryotic ancestor of tubulin, FtsZ, the major protein involved in bacterial division. Expression of S100B protein in E. coli results in little change in FtsZ protein levels, causes a filamenting bacterial phenotype characteristic of FtsZ inhibition, and leads to missed rounds of cell division. Further, S100B localizes to positions similar to those of FtsZ in bacterial filaments: the small foci at the poles, the mid-cell positions, and between the nucleoids at regular intervals. Calcium-dependent physical interaction between S100B and FtsZ was demonstrated in vitro by affinity chromatography, and this interaction was severely inhibited by the competitor peptide TRTK-12. Together these results indicate that S100B interacts with the tubulin homologue FtsZ in vivo, modulating its activity in bacterial cell division. This approach will present an important step for the study of S100 protein interactions in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human S100B Protein Interacts with the Escherichia coli Division Protein FtsZ in a Calcium-sensitive Manner

Ferguson

Shaw

2004

Journal of Biological Chemistry

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“…However, the S100b C-terminal domain is important for certain S100b/target protein interactions. [43][44][45] With this background, one possibility would be that S100b2 interacts with S100b, modulating the neurotrophic biological activities normally associated with the S100b homodimer; (ii) the S100b2 mRNA isoform is finally not translated and is produced to modulate the S100b mRNA pool, available for S100b protein production. Such hypothesis could be supported by the strong correlation existing between the S100b and S100b2 mRNA levels in the brain of AD cases.…”

Section: -42mentioning

confidence: 99%

Evidence for the association of the S100β gene with low cognitive performance and dementia in the elderly

et al. 2007

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Variations in the S100b gene may be instrumental in producing a continuum from mild cognitive decline to overt dementia. After screening 25 single nucleotide polymorphisms (SNPs) in S100b, we observed association of the rs2300403 intron 2 SNP with poorer cognitive function in three independent populations. Moreover, we detected a significant association of this SNP with increased risk of developing dementia or Alzheimer's disease (AD) in six independent populations, especially in women and in the oldest. Furthermore, we characterised a new primate-specific exon within intron 2 (the corresponding mRNA isoform was called S100b2). S100b2 expression was increased in AD brain compared with controls, and the rs2300403 SNP was associated with elevated levels of S100b2 mRNA in AD brains, especially in women. Therefore, this genetic variant in S100b increases the risk of low cognitive performance and dementia, possibly by favouring a splicing event increasing S100b2 isoform expression in the brain.

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“…We first studied the interactions of the wild-type S100B and of a C-terminal deleted mutant S100B (S100B⌬Ct) with IQGAP1 and AHNAK. We used S100B⌬Ct because the C terminus domain of S100B is required for interactions between S100B and strict Ca 2ϩ -dependent target protein (32,33). NIH 3T3 cells were transfected with expression vectors encoding S100B or S100B⌬Ct, and complex formation was assayed by co-immunoprecipitation using the N-terminal S100B monoclonal antibody S16 (Fig.…”

Section: Mechanism Of Znmentioning

confidence: 99%

The Zinc- and Calcium-binding S100B Interacts and Co-localizes with IQGAP1 during Dynamic Rearrangement of Cell Membranes

Mbele

Deloulme

Gentil

et al. 2002

Journal of Biological Chemistry

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The Zn 2؉ -and Ca 2؉ -binding S100B protein is implicated in multiple intracellular and extracellular regulatory events. In glial cells, a relationship exists between cytoplasmic S100B accumulation and cell morphological changes. We have identified the IQGAP1 protein as the major cytoplasmic S100B target protein in different rat and human glial cell lines in the presence of Zn 2؉ and Ca 2؉ . Zn 2؉ binding to S100B is sufficient to promote interaction with IQGAP1. IQ motifs on IQGAP1 represent the minimal interaction sites for S100B. We also provide evidence that, in human astrocytoma cell lines, S100B co-localizes with IQGAP1 at the polarized leading edge and areas of membrane ruffling and that both proteins relocate in a Ca 2؉ -dependent manner within newly formed vesicle-like structures. Our data identify IQ-GAP1 as a potential target protein of S100B during processes of dynamic rearrangement of cell membrane morphology. They also reveal an additional cellular function for IQGAP1 associated with Zn 2؉ /Ca 2؉ -dependent relocation of S100B. S100B is a member of the S100 family of proteins containing two EF-hand-type calcium-binding domains (1). This protein interacts not only with Ca 2ϩ but also with Zn 2ϩ ions, binding Zn 2ϩ ions with an affinity in the nanomolar range (2). The capacity of S100B to bind and release Zn 2ϩ suggests that Zn 2ϩ may not only play a structural role but might also be involved, together with Ca 2ϩ , in concerted regulation of S100B function. The S100B protein is naturally highly expressed in the vertebrate nervous system, where it is present in astrocytes and Schwann cells (3). In the adult central nervous system, the S100B protein is present in the nuclei and cytoplasm of astrocytes and accumulates in the astrocytic dendrites in the perivascular processes (4). Studies in different laboratories suggest a variety of intracellular regulations by S100B, including negative cell growth regulation (5), cell structure (6), and calcium homeostasis (7). The S100B protein is also secreted from astrocytes and has extracellular functions (8). Extracellular S100B acts as a modulator of neuronal synaptic plasticity (9). Although nanomolar quantities have beneficial neurotrophic effects on nerve cells, high levels of this protein have been implicated in glia activation and could contribute to the development of brain pathology as observed in Down's syndrome and Alzheimer's disease (10). The recent observation that S100B triggers activation of the pro-inflammatory cell surface receptor receptor for advanced glycation end products has shed more light on its extracellular function (11). In cultured human astrocytoma U87 cells, S100B secretion is dependent on relocation of S100B toward vesicle-like structures at the periphery of the cells and is regulated by Ca 2ϩ and Zn 2ϩ (12). S100B can also be secreted into the bloodstream and cerebrospinal fluid and is a biochemical marker of brain damage or dysfunction in acute and chronic diseases (13,14). A relationship between S100B accumulation in the astrocy...

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The C-Terminus and Linker Region of S100B Exert Dual Control on Protein−Protein Interactions with TRTK-12

Cited by 26 publications

References 44 publications

Human S100B Protein Interacts with the Escherichia coli Division Protein FtsZ in a Calcium-sensitive Manner

Human S100B Protein Interacts with the Escherichia coli Division Protein FtsZ in a Calcium-sensitive Manner

Evidence for the association of the S100β gene with low cognitive performance and dementia in the elderly

The Zinc- and Calcium-binding S100B Interacts and Co-localizes with IQGAP1 during Dynamic Rearrangement of Cell Membranes

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