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| | <StructureSection load='4qdr' size='340' side='right'caption='[[4qdr]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4qdr' size='340' side='right'caption='[[4qdr]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qdr]] 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=4QDR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QDR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qdr]] 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=4QDR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QDR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qdq|4qdq]], [[4qds|4qds]]</td></tr> | + | </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=4qdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qdr OCA], [https://pdbe.org/4qdr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qdr RCSB], [https://www.ebi.ac.uk/pdbsum/4qdr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qdr ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NRP2, VEGF165R2 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qdr OCA], [http://pdbe.org/4qdr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qdr RCSB], [http://www.ebi.ac.uk/pdbsum/4qdr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qdr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NRP2_HUMAN NRP2_HUMAN]] High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF. | + | [https://www.uniprot.org/uniprot/NRP2_HUMAN NRP2_HUMAN] High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kooi, C W.Vander]]
| + | [[Category: Parker MW]] |
| - | [[Category: Parker, M W]] | + | [[Category: Vander Kooi CW]] |
| - | [[Category: Cell adhesion]] | + | |
| - | [[Category: Coagulation factor domain]]
| + | |
| - | [[Category: Discoidin domain]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Vegf-c]]
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| Structural highlights
Function
NRP2_HUMAN High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.
Publication Abstract from PubMed
Vascular endothelial growth factor C (VEGF-C) is a potent lymphangiogenic cytokine that signals via the coordinated action of two cell surface receptors, Neuropilin-2 (Nrp2) and VEGFR-3. Diseases associated with both loss and gain of VEGF-C function, lymphedema and cancer, respectively, motivate studies of VEGF-C/Nrp2 binding and inhibition. Here, we demonstrate that VEGF-C binding to Nrp2 is regulated by C-terminal proteolytic maturation. The structure of the VEGF-C C terminus in complex with the ligand binding domains of Nrp2 demonstrates that a cryptic Nrp2 binding motif is released upon proteolysis, allowing specific engagement with the b1 domain of Nrp2. Based on the identified structural requirements for Nrp2 binding to VEGF-C, we hypothesized that the endogenous secreted splice form of Nrp2, s9Nrp2, may function as a selective inhibitor of VEGF-C. We find that s9Nrp2 forms a stable dimer that potently inhibits VEGF-C/Nrp2 binding and cellular signaling. These data provide critical insight into VEGF-C/Nrp2 binding and inhibition.
Structural Basis for VEGF-C Binding to Neuropilin-2 and Sequestration by a Soluble Splice Form.,Parker MW, Linkugel AD, Goel HL, Wu T, Mercurio AM, Vander Kooi CW Structure. 2015 Apr 7;23(4):677-87. doi: 10.1016/j.str.2015.01.018. Epub 2015 Mar, 5. PMID:25752543[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Parker MW, Linkugel AD, Goel HL, Wu T, Mercurio AM, Vander Kooi CW. Structural Basis for VEGF-C Binding to Neuropilin-2 and Sequestration by a Soluble Splice Form. Structure. 2015 Apr 7;23(4):677-87. doi: 10.1016/j.str.2015.01.018. Epub 2015 Mar, 5. PMID:25752543 doi:http://dx.doi.org/10.1016/j.str.2015.01.018
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