| Structural highlights
3ol2 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 3okt, 1olz |
| Gene: | SEMA4D, C9orf164, CD100, SEMAJ (HUMAN), PLXNB1, KIAA0407, PLXN5, SEP (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SEM4D_HUMAN] Cell surface receptor for PLXN1B and PLXNB2 that plays an important role in cell-cell signaling. Promotes reorganization of the actin cytoskeleton and plays a role in axonal growth cone guidance in the developing central nervous system. Regulates dendrite and axon branching and morphogenesis. Promotes the migration of cerebellar granule cells and of endothelial cells. Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro). Promotes signaling via SRC and PTK2B/PYK2, which then mediates activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Interaction with PLXNB1 mediates activation of RHOA.[1] [2] [3] [4] [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.[5] [6] [7] [8] [9] [10]
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[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Basile JR, Afkhami T, Gutkind JS. Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway. Mol Cell Biol. 2005 Aug;25(16):6889-98. PMID:16055703 doi:http://dx.doi.org/10.1128/MCB.25.16.6889-6898.2005
- ↑ Vodrazka P, Korostylev A, Hirschberg A, Swiercz JM, Worzfeld T, Deng S, Fazzari P, Tamagnone L, Offermanns S, Kuner R. The semaphorin 4D-plexin-B signalling complex regulates dendritic and axonal complexity in developing neurons via diverse pathways. Eur J Neurosci. 2009 Oct;30(7):1193-208. doi: 10.1111/j.1460-9568.2009.06934.x., Epub 2009 Sep 29. PMID:19788569 doi:http://dx.doi.org/10.1111/j.1460-9568.2009.06934.x
- ↑ 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
- ↑ Hall KT, Boumsell L, Schultze JL, Boussiotis VA, Dorfman DM, Cardoso AA, Bensussan A, Nadler LM, Freeman GJ. Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11780-5. PMID:8876214
- ↑ 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
- ↑ 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
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