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| | <StructureSection load='3okw' size='340' side='right'caption='[[3okw]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3okw' size='340' side='right'caption='[[3okw]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3okw]] is a 2 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=3OKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OKW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3okw]] is a 2 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=3OKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OKW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 2.299Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3okt|3okt]], [[3oky|3oky]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sema6a, Semaq ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3okw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3okw OCA], [https://pdbe.org/3okw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3okw RCSB], [https://www.ebi.ac.uk/pdbsum/3okw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3okw ProSAT]</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=3okw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3okw OCA], [https://pdbe.org/3okw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3okw RCSB], [https://www.ebi.ac.uk/pdbsum/3okw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3okw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SEM6A_MOUSE SEM6A_MOUSE]] Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation.<ref>PMID:16205717</ref> <ref>PMID:19063725</ref> <ref>PMID:20877282</ref> <ref>PMID:20881961</ref>
| + | [https://www.uniprot.org/uniprot/SEM6A_MOUSE SEM6A_MOUSE] Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation.<ref>PMID:16205717</ref> <ref>PMID:19063725</ref> <ref>PMID:20877282</ref> <ref>PMID:20881961</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Cell-cell signalling of semaphorin ligands through interaction with plexin receptors is important for the homeostasis and morphogenesis of many tissues and is widely studied for its role in neural connectivity, cancer, cell migration and immune responses. SEMA4D and Sema6A exemplify two diverse vertebrate, membrane-spanning semaphorin classes (4 and 6) that are capable of direct signalling through members of the two largest plexin classes, B and A, respectively. In the absence of any structural information on the plexin ectodomain or its interaction with semaphorins the extracellular specificity and mechanism controlling plexin signalling has remained unresolved. Here we present crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto). These structures, together with biophysical and cellular assays of wild-type and mutant proteins, reveal that semaphorin dimers independently bind two plexin molecules and that signalling is critically dependent on the avidity of the resulting bivalent 2:2 complex (monomeric semaphorin binds plexin but fails to trigger signalling). In combination, our data favour a cell-cell signalling mechanism involving semaphorin-stabilized plexin dimerization, possibly followed by clustering, which is consistent with previous functional data. Furthermore, the shared generic architecture of the complexes, formed through conserved contacts of the amino-terminal seven-bladed beta-propeller (sema) domains of both semaphorin and plexin, suggests that a common mode of interaction triggers all semaphorin-plexin based signalling, while distinct insertions within or between blades of the sema domains determine binding specificity.
| + | |
| - | | + | |
| - | Structural basis of semaphorin-plexin signalling.,Janssen BJ, Robinson RA, Perez-Branguli F, Bell CH, Mitchell KJ, Siebold C, Jones EY Nature. 2010 Sep 26. PMID:20877282<ref>PMID:20877282</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3okw" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bell, C H]] | + | [[Category: Bell CH]] |
| - | [[Category: Janssen, B J.C]] | + | [[Category: Janssen BJC]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Jones EY]] |
| - | [[Category: Robinson, R A]] | + | [[Category: Robinson RA]] |
| - | [[Category: Siebold, C]] | + | [[Category: Siebold C]] |
| - | [[Category: Cell-cell signalling]]
| + | |
| - | [[Category: Ligand]]
| + | |
| - | [[Category: Plexin a2]]
| + | |
| - | [[Category: Sema-domain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
3okw is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.299Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
SEM6A_MOUSE Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation.[1] [2] [3] [4]
See Also
References
- ↑ Kerjan G, Dolan J, Haumaitre C, Schneider-Maunoury S, Fujisawa H, Mitchell KJ, Chedotal A. The transmembrane semaphorin Sema6A controls cerebellar granule cell migration. Nat Neurosci. 2005 Nov;8(11):1516-24. Epub 2005 Oct 2. PMID:16205717 doi:http://dx.doi.org/10.1038/nn1555
- ↑ Runker AE, Little GE, Suto F, Fujisawa H, Mitchell KJ. Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points. Neural Dev. 2008 Dec 8;3:34. doi: 10.1186/1749-8104-3-34. PMID:19063725 doi:http://dx.doi.org/10.1186/1749-8104-3-34
- ↑ Janssen BJ, Robinson RA, Perez-Branguli F, Bell CH, Mitchell KJ, Siebold C, Jones EY. Structural basis of semaphorin-plexin signalling. Nature. 2010 Sep 26. PMID:20877282 doi:10.1038/nature09468
- ↑ Nogi T, Yasui N, Mihara E, Matsunaga Y, Noda M, Yamashita N, Toyofuku T, Uchiyama S, Goshima Y, Kumanogoh A, Takagi J. Structural basis for semaphorin signalling through the plexin receptor. Nature. 2010 Sep 29. PMID:20881961 doi:10.1038/nature09473
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