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| | ==X-ray structure of Ca(2+)-S100B with human RAGE-derived W61 peptide== | | ==X-ray structure of Ca(2+)-S100B with human RAGE-derived W61 peptide== |
| - | <StructureSection load='4xyn' size='340' side='right' caption='[[4xyn]], [[Resolution|resolution]] 2.55Å' scene=''> | + | <StructureSection load='4xyn' size='340' side='right'caption='[[4xyn]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xyn]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4n6i 4n6i]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XYN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xyn]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4n6i 4n6i]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XYN 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></td></tr> | + | </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></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])</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=4xyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xyn OCA], [https://pdbe.org/4xyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xyn RCSB], [https://www.ebi.ac.uk/pdbsum/4xyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xyn 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=4xyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xyn OCA], [http://pdbe.org/4xyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xyn RCSB], [http://www.ebi.ac.uk/pdbsum/4xyn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xyn 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> | + | [https://www.uniprot.org/uniprot/RAGE_HUMAN RAGE_HUMAN] Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.<ref>PMID:19906677</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 4xyn" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4xyn" 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: Colbert, C L]] | + | [[Category: Large Structures]] |
| - | [[Category: Indurthi, V S.K]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Jensen, J L]] | + | [[Category: Colbert CL]] |
| - | [[Category: Neau, D]] | + | [[Category: Indurthi VSK]] |
| - | [[Category: Vetter, S W]] | + | [[Category: Jensen JL]] |
| - | [[Category: Membrane protein]] | + | [[Category: Neau D]] |
| - | [[Category: Metal binding protein]] | + | [[Category: Vetter SW]] |
| Structural highlights
Function
RAGE_HUMAN Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.[1]
Publication Abstract from PubMed
S100B is a damage-associated molecular pattern protein that, when released into the extracellular milieu, triggers initiation of the inflammatory response through the receptor for advanced glycation end products (RAGE). Recognition of S100B is accomplished via the amino-terminal variable immunoglobulin domain (V-domain) of RAGE. To gain insights into this interaction, a complex between S100B and a 15-amino-acid peptide derived from residues 54-68 of the V-domain was crystallized. The X-ray crystal structure was solved to 2.55 A resolution. There are two dimers of S100B and one peptide in the asymmetric unit. The binding interface of this peptide is compared with that found in the complex between S100B and the 12-amino-acid CapZ-derived peptide TRTK-12. This comparison reveals that although the peptides adopt completely different backbone structures, the residues buried at the interface interact with S100B in similar regions to form stable complexes. The binding affinities of S100B for the intact wild-type V-domain and a W61A V-domain mutant were determined to be 2.7 +/- 0.5 and 1.3 +/- 0.7 microM, respectively, using fluorescence titration experiments. These observations lead to a model whereby conformational flexibility in the RAGE receptor allows the adoption of a binding conformation for interaction with the stable hydrophobic groove on the surface of S100B.
Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex.,Jensen JL, Indurthi VS, Neau DB, Vetter SW, Colbert CL Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1176-83. doi:, 10.1107/S1399004715004216. Epub 2015 Apr 25. PMID:25945582[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fang F, Lue LF, Yan S, Xu H, Luddy JS, Chen D, Walker DG, Stern DM, Yan S, Schmidt AM, Chen JX, Yan SS. RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease. FASEB J. 2010 Apr;24(4):1043-55. doi: 10.1096/fj.09-139634. Epub 2009 Nov 11. PMID:19906677 doi:10.1096/fj.09-139634
- ↑ Jensen JL, Indurthi VS, Neau DB, Vetter SW, Colbert CL. Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex. Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1176-83. doi:, 10.1107/S1399004715004216. Epub 2015 Apr 25. PMID:25945582 doi:http://dx.doi.org/10.1107/S1399004715004216
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