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| | ==Complex of mouse Plexin A2 - Semaphorin 3A - Neuropilin-1== | | ==Complex of mouse Plexin A2 - Semaphorin 3A - Neuropilin-1== |
| - | <StructureSection load='4gza' size='340' side='right' caption='[[4gza]], [[Resolution|resolution]] 7.00Å' scene=''> | + | <StructureSection load='4gza' size='340' side='right'caption='[[4gza]], [[Resolution|resolution]] 7.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gza]] is a 8 chain structure with sequence from [http://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=4GZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GZA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gza]] is a 8 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=4GZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GZA 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></td></tr> | + | </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></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gz8|4gz8]], [[4gz9|4gz9]]</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=4gza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gza OCA], [https://pdbe.org/4gza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gza RCSB], [https://www.ebi.ac.uk/pdbsum/4gza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gza ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Plxna2, Kiaa0463 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Sema3a, Semad, SemD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Nrp1, Nrp ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gza OCA], [http://pdbe.org/4gza PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gza RCSB], [http://www.ebi.ac.uk/pdbsum/4gza PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gza ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLXA2_MOUSE PLXA2_MOUSE]] Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.<ref>PMID:10520994</ref> <ref>PMID:10781943</ref> <ref>PMID:20877282</ref> [[http://www.uniprot.org/uniprot/NRP1_MOUSE NRP1_MOUSE]] Receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, the PLGF-2 isoform of PGF, the VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis (By similarity). [[http://www.uniprot.org/uniprot/SEM3A_MOUSE SEM3A_MOUSE]] Plays a role in growth cones guidance. May function to pattern sensory projections by selectively repelling axons that normally terminate dorsally. | + | [https://www.uniprot.org/uniprot/PLXA2_MOUSE PLXA2_MOUSE] Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.<ref>PMID:10520994</ref> <ref>PMID:10781943</ref> <ref>PMID:20877282</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | *[[Neuropilin|Neuropilin]] | | *[[Neuropilin|Neuropilin]] |
| | *[[Plexin|Plexin]] | | *[[Plexin|Plexin]] |
| - | *[[Semaphorin|Semaphorin]] | + | *[[Semaphorin 3D structures|Semaphorin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Janssen, B J.C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Janssen BJC]] |
| - | [[Category: Malinauskas, T]] | + | [[Category: Jones EY]] |
| - | [[Category: Siebold, C]] | + | [[Category: Malinauskas T]] |
| - | [[Category: Cell-cell signaling]] | + | [[Category: Siebold C]] |
| - | [[Category: Glycosilation]]
| + | |
| - | [[Category: Mammalian]]
| + | |
| - | [[Category: Multi-domain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Ternary complex]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
PLXA2_MOUSE Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.[1] [2] [3]
Publication Abstract from PubMed
Co-receptors add complexity to cell-cell signaling systems. The secreted semaphorin 3s (Sema3s) require a co-receptor, neuropilin (Nrp), to signal through plexin As (PlxnAs) in functions ranging from axon guidance to bone homeostasis, but the role of the co-receptor is obscure. Here we present the low-resolution crystal structure of a mouse semaphorin-plexin-Nrp complex alongside unliganded component structures. Dimeric semaphorin, two copies of plexin and two copies of Nrp are arranged as a dimer of heterotrimers. In each heterotrimer subcomplex, semaphorin contacts plexin, similar to in co-receptor-independent signaling complexes. The Nrp1s cross brace the assembly, bridging between sema domains of the Sema3A and PlxnA2 subunits from the two heterotrimers. Biophysical and cellular analyses confirm that this Nrp binding mode stabilizes a canonical, but weakened, Sema3-PlxnA interaction, adding co-receptor control over the mechanism by which receptor dimerization and/or oligomerization triggers signaling.
Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex.,Janssen BJ, Malinauskas T, Weir GA, Cader MZ, Siebold C, Jones EY Nat Struct Mol Biol. 2012 Dec;19(12):1293-9. doi: 10.1038/nsmb.2416. Epub 2012, Oct 28. PMID:23104057[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell. 1999 Oct 1;99(1):59-69. PMID:10520994
- ↑ Rohm B, Ottemeyer A, Lohrum M, Puschel AW. Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev. 2000 May;93(1-2):95-104. PMID:10781943
- ↑ 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
- ↑ Janssen BJ, Malinauskas T, Weir GA, Cader MZ, Siebold C, Jones EY. Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex. Nat Struct Mol Biol. 2012 Dec;19(12):1293-9. doi: 10.1038/nsmb.2416. Epub 2012, Oct 28. PMID:23104057 doi:http://dx.doi.org/10.1038/nsmb.2416
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