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| | ==Plexin A2 full extracellular region, domains 1 to 8 modeled, data to 10 angstrom== | | ==Plexin A2 full extracellular region, domains 1 to 8 modeled, data to 10 angstrom== |
| - | <StructureSection load='5l5g' size='340' side='right' caption='[[5l5g]], [[Resolution|resolution]] 10.00Å' scene=''> | + | <StructureSection load='5l5g' size='340' side='right'caption='[[5l5g]], [[Resolution|resolution]] 10.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5l5g]] is a 4 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=5L5G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L5G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5l5g]] is a 4 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=5L5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L5G FirstGlance]. <br> |
| - | </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])</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]] 10Å</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=5l5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l5g OCA], [http://pdbe.org/5l5g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l5g RCSB], [http://www.ebi.ac.uk/pdbsum/5l5g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l5g 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=5l5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l5g OCA], [https://pdbe.org/5l5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l5g RCSB], [https://www.ebi.ac.uk/pdbsum/5l5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l5g 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> | + | [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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| | ==See Also== | | ==See Also== |
| - | *[[Plexin|Plexin]] | + | *[[Plexin 3D structures|Plexin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Coles, C H]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gilbert, R J.C]] | + | [[Category: Coles CH]] |
| - | [[Category: Janssen, B J.C]] | + | [[Category: Gilbert RJC]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Janssen BJC]] |
| - | [[Category: Kaufmann, R]] | + | [[Category: Jones EY]] |
| - | [[Category: Kong, Y]] | + | [[Category: Kaufmann R]] |
| - | [[Category: Malinauskas, T]] | + | [[Category: Kong Y]] |
| - | [[Category: Ni, T]] | + | [[Category: Malinauskas T]] |
| - | [[Category: Padilla-Parra, S]] | + | [[Category: Ni T]] |
| - | [[Category: Pasterkamp, R J]] | + | [[Category: Padilla-Parra S]] |
| - | [[Category: Vangoor, V R]] | + | [[Category: Pasterkamp RJ]] |
| - | [[Category: Axon guidance]]
| + | [[Category: Vangoor VR]] |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Signaling]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| 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
Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development and plasticity, ranging from axon guidance and neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization, but extracellular regulation and activation mechanisms remain unclear. Here we present crystal structures of PlxnA (PlxnA1, PlxnA2, and PlxnA4) full ectodomains. Domains 1-9 form a ring-like conformation from which the C-terminal domain 10 points away. All our PlxnA ectodomain structures show autoinhibitory, intermolecular "head-to-stalk" (domain 1 to domain 4-5) interactions, which are confirmed by biophysical assays, live cell fluorescence microscopy, and cell-based and neuronal growth cone collapse assays. This work reveals a 2-fold role of the PlxnA ectodomains: imposing a pre-signaling autoinhibitory separation for the cytoplasmic domains via intermolecular head-to-stalk interactions and supporting dimerization-based PlxnA activation upon ligand binding. More generally, our data identify a novel molecular mechanism for preventing premature activation of axon guidance receptors.
Structural Basis for Plexin Activation and Regulation.,Kong Y, Janssen BJ, Malinauskas T, Vangoor VR, Coles CH, Kaufmann R, Ni T, Gilbert RJ, Padilla-Parra S, Pasterkamp RJ, Jones EY Neuron. 2016 Jul 5. pii: S0896-6273(16)30295-1. doi:, 10.1016/j.neuron.2016.06.018. PMID:27397516[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
- ↑ Kong Y, Janssen BJ, Malinauskas T, Vangoor VR, Coles CH, Kaufmann R, Ni T, Gilbert RJ, Padilla-Parra S, Pasterkamp RJ, Jones EY. Structural Basis for Plexin Activation and Regulation. Neuron. 2016 Jul 5. pii: S0896-6273(16)30295-1. doi:, 10.1016/j.neuron.2016.06.018. PMID:27397516 doi:http://dx.doi.org/10.1016/j.neuron.2016.06.018
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