View source for 4qdr


==Physical basis for Nrp2 ligand binding==
<StructureSection load='4qdr' size='340' side='right'caption='[[4qdr]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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>
</table>
== Function ==
[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;">
== 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<ref>PMID:25752543</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qdr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neuropilin|Neuropilin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Parker MW]]
[[Category: Vander Kooi CW]]