View source for 7ne1


==Structure of the complex between Netrin-1 and its receptor Neogenin==
<StructureSection load='7ne1' size='340' side='right'caption='[[7ne1]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ne1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NE1 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]] 3.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GU4:2,3,4,6-TETRA-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU4</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PRD_900013:sucrose+octasulfate'>PRD_900013</scene>, <scene name='pdbligand=YYJ:1,3,4,6-tetra-O-sulfo-beta-D-fructofuranose'>YYJ</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=7ne1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ne1 OCA], [https://pdbe.org/7ne1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ne1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ne1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ne1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NET1_HUMAN NET1_HUMAN] Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. It also serve as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in tumorigenesis by regulating apoptosis.<ref>PMID:15343335</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
During cell migration or differentiation, cell surface receptors are simultaneously exposed to different ligands. However, it is often unclear how these extracellular signals are integrated. Neogenin (NEO1) acts as an attractive guidance receptor when the Netrin-1 (NET1) ligand binds, but it mediates repulsion via repulsive guidance molecule (RGM) ligands. Here, we show that signal integration occurs through the formation of a ternary NEO1-NET1-RGM complex, which triggers reciprocal silencing of downstream signaling. Our NEO1-NET1-RGM structures reveal a "trimer-of-trimers" super-assembly, which exists in the cell membrane. Super-assembly formation results in inhibition of RGMA-NEO1-mediated growth cone collapse and RGMA- or NET1-NEO1-mediated neuron migration, by preventing formation of signaling-compatible RGM-NEO1 complexes and NET1-induced NEO1 ectodomain clustering. These results illustrate how simultaneous binding of ligands with opposing functions, to a single receptor, does not lead to competition for binding, but to formation of a super-complex that diminishes their functional outputs.

Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling.,Robinson RA, Griffiths SC, van de Haar LL, Malinauskas T, van Battum EY, Zelina P, Schwab RA, Karia D, Malinauskaite L, Brignani S, van den Munkhof MH, Dudukcu O, De Ruiter AA, Van den Heuvel DMA, Bishop B, Elegheert J, Aricescu AR, Pasterkamp RJ, Siebold C Cell. 2021 Apr 15;184(8):2103-2120.e31. doi: 10.1016/j.cell.2021.02.045. Epub , 2021 Mar 18. PMID:33740419<ref>PMID:33740419</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ne1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Netrin|Netrin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Aricescu AR]]
[[Category: Bishop B]]
[[Category: Brignani S]]
[[Category: De Ruiter AA]]
[[Category: Dudukcu O]]
[[Category: Elegheert J]]
[[Category: Griffiths SC]]
[[Category: Karia D]]
[[Category: Malinauskaite L]]
[[Category: Malinauskas T]]
[[Category: Pasterkamp RJ]]
[[Category: Robinson RA]]
[[Category: Schwab RA]]
[[Category: Siebold C]]
[[Category: Van den Heuvel DMA]]
[[Category: Zelina P]]
[[Category: Van Battum EY]]
[[Category: Van de Haar LL]]
[[Category: Van den Munkhof M]]