2l7u

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{{STRUCTURE_2l7u| PDB=2l7u | SCENE= }}
 
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===Structure of CEL-PEP-RAGE V domain complex===
 
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{{ABSTRACT_PUBMED_21565706}}
 
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==Function==
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==Structure of CEL-PEP-RAGE V domain complex==
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[[http://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> [[http://www.uniprot.org/uniprot/ALBU_BOVIN ALBU_BOVIN]] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
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<StructureSection load='2l7u' size='340' side='right'caption='[[2l7u]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2l7u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L7U FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KPI:(2S)-2-AMINO-6-[(1-HYDROXY-1-OXO-PROPAN-2-YLIDENE)AMINO]HEXANOIC+ACID'>KPI</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l7u OCA], [https://pdbe.org/2l7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l7u RCSB], [https://www.ebi.ac.uk/pdbsum/2l7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l7u ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Nonenzymatic protein glycation results in the formation of advanced glycation end products (AGEs) that are implicated in the pathology of diabetes, chronic inflammation, Alzheimer's disease, and cancer. AGEs mediate their effects primarily through a receptor-dependent pathway in which AGEs bind to a specific cell surface associated receptor, the Receptor for AGEs (RAGE). N(varepsilon)-carboxy-methyl-lysine (CML) and N(varepsilon)-carboxy-ethyl-lysine (CEL), constitute two of the major AGE structures found in tissue and blood plasma, and are physiological ligands of RAGE. The solution structure of a CEL-containing peptide-RAGE V domain complex reveals that the carboxyethyl moiety fits inside a positively charged cavity of the V domain. Peptide backbone atoms make specific contacts with the V domain. The geometry of the bound CEL peptide is compatible with many CML (CEL)-modified sites found in plasma proteins. The structure explains how such patterned ligands as CML (CEL)-proteins bind to RAGE and contribute to RAGE signaling.
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==About this Structure==
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Advanced glycation end product recognition by the receptor for AGEs.,Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, Burz DS, Schmidt AM, Hoffmann R, Shekhtman A Structure. 2011 May 11;19(5):722-32. PMID:21565706<ref>PMID:21565706</ref>
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[[2l7u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L7U OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:021565706</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 2l7u" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Burz, D.]]
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[[Category: Large Structures]]
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[[Category: Chabierski, S.]]
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[[Category: Burz D]]
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[[Category: Frolov, S.]]
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[[Category: Chabierski S]]
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[[Category: Hoffman, R.]]
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[[Category: Frolov S]]
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[[Category: Rai, V.]]
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[[Category: Hoffman R]]
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[[Category: Reverdatto, S.]]
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[[Category: Rai V]]
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[[Category: Schmidt, A.]]
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[[Category: Reverdatto S]]
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[[Category: Shekhtman, A.]]
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[[Category: Schmidt A]]
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[[Category: Singer, D.]]
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[[Category: Shekhtman A]]
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[[Category: Xie, J.]]
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[[Category: Singer D]]
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[[Category: Xue, J.]]
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[[Category: Xie J]]
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[[Category: Allergen]]
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[[Category: Xue J]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Lipid-binding]]
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[[Category: Metal-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Secreted]]
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[[Category: V domain]]
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Current revision

Structure of CEL-PEP-RAGE V domain complex

PDB ID 2l7u

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