4qds: Difference between revisions
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==Physical basis for Nrp2 ligand binding== | |||
<StructureSection load='4qds' size='340' side='right'caption='[[4qds]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4qds]] is a 2 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=4QDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QDS 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]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4qds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qds OCA], [https://pdbe.org/4qds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qds RCSB], [https://www.ebi.ac.uk/pdbsum/4qds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qds 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Parker | <div class="pdbe-citations 4qds" style="background-color:#fffaf0;"></div> | ||
[[Category: Vander Kooi | |||
==See Also== | |||
*[[Neuropilin|Neuropilin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Parker MW]] | |||
[[Category: Vander Kooi CW]] | |||
Latest revision as of 17:31, 20 September 2023
Physical basis for Nrp2 ligand binding
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