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2mjw

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Revision as of 07:17, 11 September 2015

Structural Insights into Calcium Bound S100P - V Domain of the receptor for advanced glycation end products (RAGE) Complex

Structural highlights

2mjw is a 4 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1j55, 2e5e
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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] [S100P_HUMAN] May stimulate cell proliferation in an autocrine manner via activation of the receptor for activated glycation end products (RAGE).^[2]

Publication Abstract from PubMed

The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE) and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+)-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC), fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2)-bound S100P was found to lie in the micromolar range (Kd of approximately 6 microM). NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.

Structural insights into calcium-bound S100P and the V domain of the RAGE complex.,Penumutchu SR, Chou RH, Yu C PLoS One. 2014 Aug 1;9(8):e103947. doi: 10.1371/journal.pone.0103947. eCollection, 2014. PMID:25084534^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Arumugam T, Simeone DM, Schmidt AM, Logsdon CD. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem. 2004 Feb 13;279(7):5059-65. Epub 2003 Nov 14. PMID:14617629 doi:http://dx.doi.org/10.1074/jbc.M310124200
↑ Penumutchu SR, Chou RH, Yu C. Structural insights into calcium-bound S100P and the V domain of the RAGE complex. PLoS One. 2014 Aug 1;9(8):e103947. doi: 10.1371/journal.pone.0103947. eCollection, 2014. PMID:25084534 doi:http://dx.doi.org/10.1371/journal.pone.0103947

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mjw"

Categories: Rao, P S | S100p v domain of rage | Signaling protein-metal binding protein complex

@@ Line 4: / Line 4: @@
 <table><tr><td colspan='2'>[[2mjw]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MJW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MJW FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j55|1j55]], [[2e5e|2e5e]]</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=2mjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mjw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mjw RCSB], [http://www.ebi.ac.uk/pdbsum/2mjw PDBsum]</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=2mjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mjw OCA], [http://pdbe.org/2mjw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mjw RCSB], [http://www.ebi.ac.uk/pdbsum/2mjw PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2mjw" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2mjw

From Proteopedia

Revision as of 07:17, 11 September 2015

Structural Insights into Calcium Bound S100P - V Domain of the receptor for advanced glycation end products (RAGE) Complex

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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