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| <StructureSection load='1wmg' size='340' side='right'caption='[[1wmg]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1wmg' size='340' side='right'caption='[[1wmg]], [[Resolution|resolution]] 2.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[1wmg]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WMG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1wmg]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WMG FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO3:SULFITE+ION'>SO3</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]] 2.1Å</td></tr> |
- | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO3:SULFITE+ION'>SO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1wmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wmg OCA], [https://pdbe.org/1wmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wmg RCSB], [https://www.ebi.ac.uk/pdbsum/1wmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wmg ProSAT], [https://www.topsan.org/Proteins/RSGI/1wmg TOPSAN]</span></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=1wmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wmg OCA], [https://pdbe.org/1wmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wmg RCSB], [https://www.ebi.ac.uk/pdbsum/1wmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wmg ProSAT], [https://www.topsan.org/Proteins/RSGI/1wmg TOPSAN]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/UNC5B_MOUSE UNC5B_MOUSE]] Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity).<ref>PMID:15729359</ref>
| + | [https://www.uniprot.org/uniprot/UNC5B_MOUSE UNC5B_MOUSE] Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity).<ref>PMID:15729359</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
- | [[Category: Handa, N]] | + | [[Category: Handa N]] |
- | [[Category: Murayama, K]] | + | [[Category: Murayama K]] |
- | [[Category: Structural genomic]]
| + | [[Category: Shirouzu M]] |
- | [[Category: Shirouzu, M]] | + | [[Category: Yokoyama S]] |
- | [[Category: Yokoyama, S]] | + | |
- | [[Category: Apoptosis]]
| + | |
- | [[Category: Death domain]]
| + | |
- | [[Category: National project on protein structural and functional analyse]]
| + | |
- | [[Category: Nppsfa]]
| + | |
- | [[Category: Rsgi]]
| + | |
- | [[Category: Six helix bundle]]
| + | |
| Structural highlights
Function
UNC5B_MOUSE Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
UNC5Hs (UNC5H1-4) are netrin 1 receptors that are involved in axonal guidance and neuronal migration. They are dependence receptors that mediate apoptosis in the absence of netrin 1. UNC5H2-induced apoptosis depends on the interaction of the death domain at the C-terminus with the DAP-kinase death domain and caspase cleavage near the transmembrane region. Here, the crystal structure of the mouse UNC5H2 death domain has been determined at 2.1 A resolution. The domain adopts a six-helix bundle fold, which is similar to those of the other members of the death-domain superfamily. The UNC5H2 death domain is a dimer in the crystal and in solution. This homodimerized structure may represent the structure of the death domain when netrin 1 binds to the UNC5H2 receptor. Homodimerization of UNC5H2 may block the access of caspase to the cleavage site. In the death-domain dimer, residues in alpha3 and the 3(10)-helix preceding alpha3 and the residues in alpha4 make significant contacts, mainly by hydrophobic and van der Waals interactions.
Structure of the UNC5H2 death domain.,Handa N, Kukimoto-Niino M, Akasaka R, Murayama K, Terada T, Inoue M, Yabuki T, Aoki M, Seki E, Matsuda T, Nunokawa E, Tanaka A, Hayashizaki Y, Kigawa T, Shirouzu M, Yokoyama S Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1502-9. Epub 2006, Nov 23. PMID:17139086[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Llambi F, Lourenco FC, Gozuacik D, Guix C, Pays L, Del Rio G, Kimchi A, Mehlen P. The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase. EMBO J. 2005 Mar 23;24(6):1192-201. Epub 2005 Feb 24. PMID:15729359 doi:http://dx.doi.org/10.1038/sj.emboj.7600584
- ↑ Handa N, Kukimoto-Niino M, Akasaka R, Murayama K, Terada T, Inoue M, Yabuki T, Aoki M, Seki E, Matsuda T, Nunokawa E, Tanaka A, Hayashizaki Y, Kigawa T, Shirouzu M, Yokoyama S. Structure of the UNC5H2 death domain. Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1502-9. Epub 2006, Nov 23. PMID:17139086 doi:10.1107/S0907444906039369
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