2n0x
From Proteopedia
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==Three dimensional structure of EPI-X4, a human albumin-derived peptide that regulates innate immunity through the CXCR4/CXCL12 chemotactic axis and antagonizes HIV-1 entry== | ==Three dimensional structure of EPI-X4, a human albumin-derived peptide that regulates innate immunity through the CXCR4/CXCL12 chemotactic axis and antagonizes HIV-1 entry== | ||
| - | <StructureSection load='2n0x' size='340' side='right' caption='[[2n0x | + | <StructureSection load='2n0x' size='340' side='right'caption='[[2n0x]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2n0x]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2n0x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N0X FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2n0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n0x OCA], [https://pdbe.org/2n0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n0x RCSB], [https://www.ebi.ac.uk/pdbsum/2n0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n0x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[https://omim.org/entry/103600 103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.<ref>PMID:8048949</ref> <ref>PMID:7852505</ref> <ref>PMID:9329347</ref> <ref>PMID:9589637</ref> |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] 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.<ref>PMID:19021548</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation. | ||
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| + | Discovery and characterization of an endogenous CXCR4 antagonist.,Zirafi O, Kim KA, Standker L, Mohr KB, Sauter D, Heigele A, Kluge SF, Wiercinska E, Chudziak D, Richter R, Moepps B, Gierschik P, Vas V, Geiger H, Lamla M, Weil T, Burster T, Zgraja A, Daubeuf F, Frossard N, Hachet-Haas M, Heunisch F, Reichetzeder C, Galzi JL, Perez-Castells J, Canales-Mayordomo A, Jimenez-Barbero J, Gimenez-Gallego G, Schneider M, Shorter J, Telenti A, Hocher B, Forssmann WG, Bonig H, Kirchhoff F, Munch J Cell Rep. 2015 May 5;11(5):737-47. doi: 10.1016/j.celrep.2015.03.061. Epub 2015, Apr 23. PMID:25921529<ref>PMID:25921529</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2n0x" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Canales | + | [[Category: Large Structures]] |
| - | [[Category: Gimenez-Gallego | + | [[Category: Canales A]] |
| - | [[Category: Jimenez-Barbero | + | [[Category: Gimenez-Gallego G]] |
| - | [[Category: Perez-Castells | + | [[Category: Jimenez-Barbero J]] |
| - | + | [[Category: Perez-Castells J]] | |
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Current revision
Three dimensional structure of EPI-X4, a human albumin-derived peptide that regulates innate immunity through the CXCR4/CXCL12 chemotactic axis and antagonizes HIV-1 entry
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