|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3sua' size='340' side='right'caption='[[3sua]], [[Resolution|resolution]] 4.39Å' scene=''> | | <StructureSection load='3sua' size='340' side='right'caption='[[3sua]], [[Resolution|resolution]] 4.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3sua]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SUA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SUA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3sua]] is a 6 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=3SUA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SUA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 4.39Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3su8|3su8]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAC1, TC25, MIG5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PLXNB1, KIAA0407, PLXN5, SEP ([https://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=3sua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sua OCA], [https://pdbe.org/3sua PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sua RCSB], [https://www.ebi.ac.uk/pdbsum/3sua PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sua 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=3sua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sua OCA], [https://pdbe.org/3sua PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sua RCSB], [https://www.ebi.ac.uk/pdbsum/3sua PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sua ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RAC1_HUMAN RAC1_HUMAN]] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> [[https://www.uniprot.org/uniprot/PLXB1_HUMAN PLXB1_HUMAN]] Receptor for SEMA4D. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.<ref>PMID:12198496</ref> <ref>PMID:12196628</ref> <ref>PMID:15210733</ref> <ref>PMID:19843518</ref> <ref>PMID:20877282</ref> <ref>PMID:21912513</ref>
| + | [https://www.uniprot.org/uniprot/PLXB1_HUMAN PLXB1_HUMAN] Receptor for SEMA4D. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.<ref>PMID:12198496</ref> <ref>PMID:12196628</ref> <ref>PMID:15210733</ref> <ref>PMID:19843518</ref> <ref>PMID:20877282</ref> <ref>PMID:21912513</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Plexins are cell surface receptors for the semaphorin family of cell guidance cues. The cytoplasmic region comprises a Ras GTPase-activating protein (GAP) domain and a RhoGTPase binding domain. Concomitant binding of extracellular semaphorin and intracellular RhoGTPase triggers GAP activity and signal transduction. The mechanism of this intricate regulation remains elusive. We present two crystal structures of the human Plexin-B1 cytoplasmic region in complex with a constitutively active RhoGTPase, Rac1. The structure of truncated Plexin-B1-Rac1 complex provides no mechanism for coupling RhoGTPase and Ras binding sites. On inclusion of the juxtamembrane helix, a trimeric structure of Plexin-B1-Rac1 complexes is stabilised by a second, novel, RhoGTPase binding site adjacent to the Ras site. Site-directed mutagenesis combined with cellular and biophysical assays demonstrate that this new binding site is essential for signalling. Our findings are consistent with a model in which extracellular and intracellular plexin clustering events combine into a single signalling output.
| + | |
| - | | + | |
| - | A Dual Binding Mode for RhoGTPases in Plexin Signalling.,Bell CH, Aricescu AR, Jones EY, Siebold C PLoS Biol. 2011 Aug;9(8):e1001134. Epub 2011 Aug 30. PMID:21912513<ref>PMID:21912513</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3sua" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Plexin|Plexin]] | + | *[[Plexin 3D structures|Plexin 3D structures]] |
| | *[[Rac 3D structures|Rac 3D structures]] | | *[[Rac 3D structures|Rac 3D structures]] |
| | == References == | | == References == |
| Line 28: |
Line 18: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aricescu, A R]] | + | [[Category: Aricescu AR]] |
| - | [[Category: Bell, C H]] | + | [[Category: Bell CH]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Jones EY]] |
| - | [[Category: Siebold, C]] | + | [[Category: Siebold C]] |
| - | [[Category: Apoptosis-signaling protein complex]]
| + | |
| - | [[Category: Axon guidance]]
| + | |
| - | [[Category: Signal transduction]]
| + | |
| Structural highlights
Function
PLXB1_HUMAN Receptor for SEMA4D. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L, Comoglio PM. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol. 2002 Sep;4(9):720-4. PMID:12198496 doi:10.1038/ncb843
- ↑ Aurandt J, Vikis HG, Gutkind JS, Ahn N, Guan KL. The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12085-90. Epub 2002 Aug 26. PMID:12196628 doi:10.1073/pnas.142433199
- ↑ Swiercz JM, Kuner R, Offermanns S. Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol. 2004 Jun 21;165(6):869-80. PMID:15210733 doi:10.1083/jcb.200312094
- ↑ Tong Y, Hota PK, Penachioni JY, Hamaneh MB, Kim S, Alviani RS, Shen L, He H, Tempel W, Tamagnone L, Park HW, Buck M. Structure and function of the intracellular region of the plexin-b1 transmembrane receptor. J Biol Chem. 2009 Dec 18;284(51):35962-72. Epub . PMID:19843518 doi:10.1074/jbc.M109.056275
- ↑ 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
- ↑ Bell CH, Aricescu AR, Jones EY, Siebold C. A Dual Binding Mode for RhoGTPases in Plexin Signalling. PLoS Biol. 2011 Aug;9(8):e1001134. Epub 2011 Aug 30. PMID:21912513 doi:10.1371/journal.pbio.1001134
|
