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| | ==THE CRYSTAL STRUCTURE OF A FRAGMENT OF NETRIN-1 IN COMPLEX WITH A FRAGMENT OF DRAXIN== | | ==THE CRYSTAL STRUCTURE OF A FRAGMENT OF NETRIN-1 IN COMPLEX WITH A FRAGMENT OF DRAXIN== |
| - | <StructureSection load='6fkq' size='340' side='right' caption='[[6fkq]], [[Resolution|resolution]] 3.07Å' scene=''> | + | <StructureSection load='6fkq' size='340' side='right'caption='[[6fkq]], [[Resolution|resolution]] 3.07Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6fkq]] is a 2 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=6FKQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FKQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fkq]] 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=6FKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FKQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.07Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4urt|4urt]]</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NTN1, NTN1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DRAXIN, C1orf187, PSEC0258, UNQ3119/PRO10268 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6fkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fkq OCA], [https://pdbe.org/6fkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fkq RCSB], [https://www.ebi.ac.uk/pdbsum/6fkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fkq ProSAT]</span></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=6fkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fkq OCA], [http://pdbe.org/6fkq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fkq RCSB], [http://www.ebi.ac.uk/pdbsum/6fkq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fkq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/DRAXI_HUMAN DRAXI_HUMAN]] Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures. Acts as a chemorepulsive guidance protein for commissural axons during development. Able to inhibit or repel neurite outgrowth from dorsal spinal cord. Inhibits the stabilization of cytosolic beta-catenin (CTNNB1) via its interaction with LRP6, thereby acting as an antagonist of Wnt signaling pathway.[HAMAP-Rule:MF_03060] | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6fkq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6fkq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Netrin|Netrin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bhowmick, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Meijers, R]] | + | [[Category: Bhowmick T]] |
| - | [[Category: Axon guidance cue]] | + | [[Category: Meijers R]] |
| - | [[Category: Commissural neuron]]
| + | |
| - | [[Category: Draxin]]
| + | |
| - | [[Category: Netrin-1]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
6fkq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3.07Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.[1]
Publication Abstract from PubMed
Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netrin-1 complexes, revealing a triangular relationship that affects Netrin-mediated haptotaxis and fasciculation. Draxin interacts with DCC through the N-terminal four immunoglobulin domains, and Netrin-1 through the EGF-3 domain, in the same region where DCC binds. Netrin-1 and DCC bind to adjacent sites on Draxin, which appears to capture Netrin-1 and tether it to the DCC receptor. We propose the conformational flexibility of the single-pass membrane receptor DCC is used to promote fasciculation and regulate axon guidance through concerted Netrin-1/Draxin binding.
Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC.,Liu Y, Bhowmick T, Liu Y, Gao X, Mertens HDT, Svergun DI, Xiao J, Zhang Y, Wang JH, Meijers R Neuron. 2018 Feb 20. pii: S0896-6273(18)30109-0. doi:, 10.1016/j.neuron.2018.02.010. PMID:29503192[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mazelin L, Bernet A, Bonod-Bidaud C, Pays L, Arnaud S, Gespach C, Bredesen DE, Scoazec JY, Mehlen P. Netrin-1 controls colorectal tumorigenesis by regulating apoptosis. Nature. 2004 Sep 2;431(7004):80-4. PMID:15343335 doi:http://dx.doi.org/10.1038/nature02788
- ↑ Liu Y, Bhowmick T, Liu Y, Gao X, Mertens HDT, Svergun DI, Xiao J, Zhang Y, Wang JH, Meijers R. Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC. Neuron. 2018 Feb 20. pii: S0896-6273(18)30109-0. doi:, 10.1016/j.neuron.2018.02.010. PMID:29503192 doi:http://dx.doi.org/10.1016/j.neuron.2018.02.010
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