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| | ==Angiopoietin-2 fibrinogen domain TAG mutant== | | ==Angiopoietin-2 fibrinogen domain TAG mutant== |
| - | <StructureSection load='4jzc' size='340' side='right' caption='[[4jzc]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4jzc' size='340' side='right'caption='[[4jzc]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jzc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JZC FirstGlance]. <br> | + | <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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gy5|2gy5]], [[1z3s|1z3s]], [[1z3u|1z3u]]</td></tr> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANGPT2 ([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=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> |
| - | <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=4jzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jzc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jzc RCSB], [http://www.ebi.ac.uk/pdbsum/4jzc PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4jzc" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Barton, W A]] | + | [[Category: Large Structures]] |
| - | [[Category: Dalton, A C]] | + | [[Category: Barton WA]] |
| - | [[Category: Goldgur, Y]] | + | [[Category: Dalton AC]] |
| - | [[Category: Nikolov, D B]] | + | [[Category: Goldgur Y]] |
| - | [[Category: Seegar, T C.M]] | + | [[Category: Nikolov DB]] |
| - | [[Category: Tzvetkova-Robev, D]] | + | [[Category: Seegar TCM]] |
| - | [[Category: Yu, X]] | + | [[Category: Tzvetkova-Robev D]] |
| - | [[Category: Fibrinogen-like receptor-binding domain]]
| + | [[Category: Yu X]] |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Tie2]]
| + | |
| - | [[Category: Tie2 receptor-binding]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997 Jul 4;277(5322):55-60. PMID:9204896
- ↑ Lee HJ, Cho CH, Hwang SJ, Choi HH, Kim KT, Ahn SY, Kim JH, Oh JL, Lee GM, Koh GY. Biological characterization of angiopoietin-3 and angiopoietin-4. FASEB J. 2004 Aug;18(11):1200-8. PMID:15284220 doi:10.1096/fj.03-1466com
- ↑ Yacyshyn OK, Lai PF, Forse K, Teichert-Kuliszewska K, Jurasz P, Stewart DJ. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0. Epub 2009 Jan 1. PMID:19116766 doi:10.1007/s10456-008-9126-0
- ↑ Yuan HT, Khankin EV, Karumanchi SA, Parikh SM. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol. 2009 Apr;29(8):2011-22. doi: 10.1128/MCB.01472-08. Epub 2009 Feb, 17. PMID:19223473 doi:10.1128/MCB.01472-08
- ↑ Yu X, Seegar TC, Dalton AC, Tzvetkova-Robev D, Goldgur Y, Rajashankar KR, Nikolov DB, Barton WA. Structural basis for angiopoietin-1-mediated signaling initiation. 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 doi:http://dx.doi.org/10.1073/pnas.1216890110
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