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| | ==S100B-RSK1 crystal structure B== | | ==S100B-RSK1 crystal structure B== |
| - | <StructureSection load='5csj' size='340' side='right' caption='[[5csj]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='5csj' size='340' side='right'caption='[[5csj]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5csj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CSJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5csj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CSJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CSJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S100B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RPS6KA1, MAPKAPK1A, RSK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5csj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5csj OCA], [https://pdbe.org/5csj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5csj RCSB], [https://www.ebi.ac.uk/pdbsum/5csj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5csj ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5csj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5csj OCA], [http://pdbe.org/5csj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5csj RCSB], [http://www.ebi.ac.uk/pdbsum/5csj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5csj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/S100B_HUMAN S100B_HUMAN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.<ref>PMID:20351179</ref> [[http://www.uniprot.org/uniprot/KS6A1_HUMAN KS6A1_HUMAN]] Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression.<ref>PMID:9430688</ref> <ref>PMID:10679322</ref> <ref>PMID:11684016</ref> <ref>PMID:12213813</ref> <ref>PMID:15117958</ref> <ref>PMID:15342917</ref> <ref>PMID:16213824</ref> <ref>PMID:16223362</ref> <ref>PMID:16763566</ref> <ref>PMID:17360704</ref> <ref>PMID:18722121</ref> | + | [https://www.uniprot.org/uniprot/S100B_HUMAN S100B_HUMAN] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.<ref>PMID:20351179</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5csj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5csj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[S100 proteins 3D structures|S100 proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Gogl, G]] | + | [[Category: Gogl G]] |
| - | [[Category: Nyitray, L]] | + | [[Category: Nyitray L]] |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: S100]]
| + | |
| - | [[Category: Signaling]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
S100B_HUMAN Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.[1]
Publication Abstract from PubMed
Mitogen-activated protein kinases (MAPK) promote MAPK activated protein kinase (MAPKAPK) activation. In the MAPK pathway responsible to cell growth, ERK2 initiates the first phosphorylation event on RSK1, which is inhibited by calcium-binding S100 proteins in malignant melanomas. Here we present a detailed in vitro biochemical and structural characterization of the S100B-RSK1 interaction. The calcium-dependent binding of S100B to the calcium/calmodulin dependent protein kinase (CaMK)-type domain of RSK1 is reminiscent to the better known binding of calmodulin to CaMKII. Although S100B-RSK1 and the calmodulin-CAMKII system are clearly distinct functionally, they demonstrate how unrelated intracellular Ca2+ binding proteins could influence the activity of CaMK domain containing protein kinases. Our crystallographic, small angle X-ray scattering (SAXS) and NMR analysis revealed that S100B forms a fuzzy complex with RSK1 peptide ligands. Based on fast-kinetics experiments we conclude that the binding involves both conformation selection and induced fit steps. Knowledge of the structural basis of this interaction could facilitate therapeutic targeting of melanomas.
Structural basis of Ribosomal S6 Kinase 1 (RSK1) inhibition by S100B Protein: modulation of the Extracellular Signal-regulated Kinase (ERK) signaling cascade in a calcium-dependent way.,Gogl G, Alexa A, Kiss B, Katona G, Kovacs M, Bodor A, Remenyi A, Nyitray L J Biol Chem. 2015 Nov 2. pii: jbc.M115.684928. PMID:26527685[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gilquin B, Cannon BR, Hubstenberger A, Moulouel B, Falk E, Merle N, Assard N, Kieffer S, Rousseau D, Wilder PT, Weber DJ, Baudier J. The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A. Mol Cell Biol. 2010 Jun;30(11):2724-36. doi: 10.1128/MCB.01468-09. Epub 2010 Mar , 29. PMID:20351179 doi:10.1128/MCB.01468-09
- ↑ Gogl G, Alexa A, Kiss B, Katona G, Kovacs M, Bodor A, Remenyi A, Nyitray L. Structural basis of Ribosomal S6 Kinase 1 (RSK1) inhibition by S100B Protein: modulation of the Extracellular Signal-regulated Kinase (ERK) signaling cascade in a calcium-dependent way. J Biol Chem. 2015 Nov 2. pii: jbc.M115.684928. PMID:26527685 doi:http://dx.doi.org/10.1074/jbc.M115.684928
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