View source for 8edi


==Structure of C. elegans UNC-5 IG 1+2 Domains bound to Heparin dp4==
<StructureSection load='8edi' size='340' side='right'caption='[[8edi]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8edi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EDI 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]] 2.11&#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=8edi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8edi OCA], [https://pdbe.org/8edi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8edi RCSB], [https://www.ebi.ac.uk/pdbsum/8edi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8edi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UNC5_CAEEL UNC5_CAEEL] Receptor for netrin (unc-6) required for axon guidance (PubMed:11454756, PubMed:8332188). Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (PubMed:11454756, PubMed:1384987, PubMed:8332188, PubMed:9473333). Axon migration is mediated by the secreted unc-6, which promotes attraction of neurons and axons through binding to the unc-40 receptor, while repulsion requires both unc-5 and unc-40 receptors (PubMed:11454756, PubMed:9473333). Involved in the ventral-dorsal and anterior-posterior migration of distal tip cells along the body, which may be mediated by Wnt receptor mom-5, ced-10/Rac, ced-12/ELMO and mig-2/RhoG (PubMed:10631179, PubMed:17716643, PubMed:26292279).<ref>PMID:10631179</ref> <ref>PMID:11454756</ref> <ref>PMID:1384987</ref> <ref>PMID:17716643</ref> <ref>PMID:26292279</ref> <ref>PMID:8332188</ref> <ref>PMID:9473333</ref> 
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== Publication Abstract from PubMed ==
Netrins dictate attractive and repulsive responses during axon growth and cell migration, where the presence of the receptor Uncoordinated-5 (UNC-5) on target cells results in repulsion. Here, we showed that UNC-5 is a heparin-binding protein, determined its structure bound to a heparin fragment, and could modulate UNC-5-heparin affinity using a directed evolution platform or structure-based rational design. We demonstrated that UNC-5 and UNC-6/netrin form a large, stable, and rigid complex in the presence of heparin, and heparin and UNC-5 exclude the attractive UNC-40/DCC receptor from binding to UNC-6/netrin to a large extent. Caenorhabditis elegans with a heparin-binding-deficient UNC-5 fail to establish proper gonad morphology due to abrogated cell migration, which relies on repulsive UNC-5 signaling in response to UNC-6. Combining UNC-5 mutations targeting heparin and UNC-6/netrin contacts results in complete cell migration and axon guidance defects. Our findings establish repulsive netrin responses to be mediated through a glycosaminoglycan-regulated macromolecular complex.

Structural insights into the formation of repulsive netrin guidance complexes.,Priest JM, Nichols EL, Smock RG, Hopkins JB, Mendoza JL, Meijers R, Shen K, Ozkan E Sci Adv. 2024 Feb 16;10(7):eadj8083. doi: 10.1126/sciadv.adj8083. Epub 2024 Feb , 16. PMID:38363837<ref>PMID:38363837</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8edi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Netrin receptor|Netrin receptor]]
== References ==
<references/>
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</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Large Structures]]
[[Category: Ozkan E]]
[[Category: Priest JM]]