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5e6p

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Revision as of 11:31, 25 December 2019

PlexinB2 cytoplasmic region/PDZ-RhoGEF PDZ domain complex

Structural highlights

5e6p is a 2 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Plxnb2 (LK3 transgenic mice), ARHGEF11, KIAA0380 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PLXB2_MOUSE] Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling. Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development. Regulates the migration of cerebellar granule cells in the developing brain. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. May modulate the activity of RAC1 and CDC42. Down-regulates macrophage migration in wound-healing assays (in vitro).^[1] ^[2] ^[3] ^[4] [ARHGB_HUMAN] May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.

Publication Abstract from PubMed

PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligands in the cell. Plexins are transmembrane receptors that regulate processes such as axon guidance and angiogenesis. Two related guanine nucleotide exchange factors (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B plexins and play critical roles in signaling. Here, we present the crystal structure of the full-length cytoplasmic region of PlexinB2 in complex with the PDZ domain of PDZ-RhoGEF. The structure reveals that, in addition to the canonical C-terminal motif/PDZ interaction, the 3D domain of PlexinB2 forms a secondary interface with the PDZ domain. Our biophysical and cell-based assays show that the secondary interface contributes to the specific interaction between plexin and PDZ-RhoGEF and to signaling by plexin in the cell. Formation of secondary interfaces may be a general mechanism for increasing affinity and specificity of modular domain-mediated interactions.

Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.,Pascoe HG, Gutowski S, Chen H, Brautigam CA, Chen Z, Sternweis PC, Zhang X Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14852-7. doi:, 10.1073/pnas.1508931112. Epub 2015 Nov 16. PMID:26627240^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Deng S, Hirschberg A, Worzfeld T, Penachioni JY, Korostylev A, Swiercz JM, Vodrazka P, Mauti O, Stoeckli ET, Tamagnone L, Offermanns S, Kuner R. Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo. J Neurosci. 2007 Jun 6;27(23):6333-47. PMID:17554007 doi:http://dx.doi.org/10.1523/JNEUROSCI.5381-06.2007
↑ Hirschberg A, Deng S, Korostylev A, Paldy E, Costa MR, Worzfeld T, Vodrazka P, Wizenmann A, Gotz M, Offermanns S, Kuner R. Gene deletion mutants reveal a role for semaphorin receptors of the plexin-B family in mechanisms underlying corticogenesis. Mol Cell Biol. 2010 Feb;30(3):764-80. doi: 10.1128/MCB.01458-09. Epub 2009 Nov, 30. PMID:19948886 doi:http://dx.doi.org/10.1128/MCB.01458-09
↑ Maier V, Jolicoeur C, Rayburn H, Takegahara N, Kumanogoh A, Kikutani H, Tessier-Lavigne M, Wurst W, Friedel RH. Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development. Mol Cell Neurosci. 2011 Feb;46(2):419-31. doi: 10.1016/j.mcn.2010.11.005. Epub, 2010 Nov 29. PMID:21122816 doi:http://dx.doi.org/10.1016/j.mcn.2010.11.005
↑ Roney KE, O'Connor BP, Wen H, Holl EK, Guthrie EH, Davis BK, Jones SW, Jha S, Sharek L, Garcia-Mata R, Bear JE, Ting JP. Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation. PLoS One. 2011;6(9):e24795. doi: 10.1371/journal.pone.0024795. Epub 2011 Sep 23. PMID:21966369 doi:http://dx.doi.org/10.1371/journal.pone.0024795
↑ Pascoe HG, Gutowski S, Chen H, Brautigam CA, Chen Z, Sternweis PC, Zhang X. Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF. Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14852-7. doi:, 10.1073/pnas.1508931112. Epub 2015 Nov 16. PMID:26627240 doi:http://dx.doi.org/10.1073/pnas.1508931112

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e6p"

@@ Line 1: / Line 1: @@
 ==PlexinB2 cytoplasmic region/PDZ-RhoGEF PDZ domain complex==
-<StructureSection load='5e6p' size='340' side='right' caption='[[5e6p]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
+<StructureSection load='5e6p' size='340' side='right'caption='[[5e6p]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5e6p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=5E6P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E6P FirstGlance]. <br>
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 5e6p" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Plexin|Plexin]]
+*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
 == References ==
 <references/>
@@ Line 23: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Pascoe, H G]]

5e6p

From Proteopedia

Revision as of 11:31, 25 December 2019

PlexinB2 cytoplasmic region/PDZ-RhoGEF PDZ domain complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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