4jzc
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4jzc is ON HOLD Authors: Yu, X., Seegar, T.C.M., Dalton, A.C., Tzvetkova-Robev, D., Goldgur, Y., Nikolov, D.B., Barton, W.A. Description: Angiopoie...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Angiopoietin-2 fibrinogen domain TAG mutant== | |
| + | <StructureSection load='4jzc' size='340' side='right'caption='[[4jzc]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4jzc]] is a 1 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=4JZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JZC FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=4jzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jzc OCA], [https://pdbe.org/4jzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jzc RCSB], [https://www.ebi.ac.uk/pdbsum/4jzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jzc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ANGP2_HUMAN ANGP2_HUMAN] Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.<ref>PMID:9204896</ref> <ref>PMID:15284220</ref> <ref>PMID:19116766</ref> <ref>PMID:19223473</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Angiogenesis is a complex cellular process involving multiple regulatory growth factors and growth factor receptors. Among them, the ligands for the endothelial-specific tunica intima endothelial receptor tyrosine kinase 2 (Tie2) receptor kinase, angiopoietin-1 (Ang1) and Ang2, play essential roles in balancing vessel stability and regression during both developmental and tumor-induced angiogenesis. Despite possessing a high degree of sequence identity, Ang1 and Ang2 have distinct functional roles and cell-signaling characteristics. Here, we present the crystal structures of Ang1 both unbound and in complex with the Tie2 ectodomain. Comparison of the Ang1-containing structures with their Ang2-containing counterparts provide insight into the mechanism of receptor activation and reveal molecular surfaces important for interactions with Tie2 coreceptors and associated signaling proteins. Using structure-based mutagenesis, we identify a loop within the angiopoietin P domain, adjacent to the receptor-binding interface, which confers the specific agonist/antagonist properties of the molecule. We demonstrate using cell-based assays that an Ang2 chimera containing the Ang1 loop sequence behaves functionally similarly to Ang1 as a constitutive Tie2 agonist, able to efficiently dissociate the inhibitory Tie1/Tie2 complex and elicit Tie2 clustering and downstream signaling. | ||
| - | + | Structural basis for angiopoietin-1-mediated signaling initiation.,Yu X, Seegar TC, Dalton AC, Tzvetkova-Robev D, Goldgur Y, Rajashankar KR, Nikolov DB, Barton WA Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7205-10. doi:, 10.1073/pnas.1216890110. Epub 2013 Apr 16. PMID:23592718<ref>PMID:23592718</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4jzc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Barton WA]] | ||
| + | [[Category: Dalton AC]] | ||
| + | [[Category: Goldgur Y]] | ||
| + | [[Category: Nikolov DB]] | ||
| + | [[Category: Seegar TCM]] | ||
| + | [[Category: Tzvetkova-Robev D]] | ||
| + | [[Category: Yu X]] | ||
Current revision
Angiopoietin-2 fibrinogen domain TAG mutant
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