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4rtt

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Revision as of 09:09, 22 November 2017

Cyrstal structure of SLIT-ROBO Rho GTPase-activating protein 2 fragment

Structural highlights

4rtt 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:	4rug
Gene:	SRGAP2, ARHGAP34, FNBP2, KIAA0456, SRGAP2A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SRGP2_HUMAN] A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13).

Function

[SRGP2_HUMAN] RAC1 GTPase activating protein (GAP) that binds and deforms membranes, and regulates actin dynamics to regulate cell migration and differentiation. Plays an important role in different aspects of neuronal morphogenesis and migration mainly during development of the cerebral cortex. This includes the biogenesis of neurites, where it is required for both axons and dendrites outgrowth, and the maturation of the dendritic spines. Also stimulates the branching of the leading process and negatively regulates neuron radial migration in the cerebral cortex. Its interaction and inhibition by SRGAP2C reduces the rate of spine maturation, alters dendritic spine morphology and density and indirectly increases neuronal migration. It may have implications for cognition, learning and memory. In non-neuronal cells, it may also play a role in cell migration by regulating the formation of lamellipodia and filopodia.^[1] ^[2] ^[3]

Publication Abstract from PubMed

srGAP proteins regulate cell migration and morphogenesis by shaping the structure and dynamics of the cytoskeleton and membranes. First discovered as intracellular effectors for the Robo1 axon-guidance receptor, srGAPs were later identified as interacting with several other nuclear and cytoplasmic proteins. In all these cases, the srGAP SH3 domain mediates protein-protein interactions by recognizing a short proline-rich segment on the cognate-binding partner. However, as interactions between the isolated SH3 domain and a selected set of ligands show weak affinity and low specificity, it is not clear how srGAPs are precisely recruited to their signaling sites. Here, we report a two-component molecular mechanism that regulates ligand binding to srGAP2 by on the one hand dramatically tightening their association and on the other, moderately autoinhibiting and restricting binding. Our results allow the design of point mutations for better probing of srGAP2 activities, and may facilitate the identification of new srGAP2 ligands.

The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism.,Guez-Haddad J, Sporny M, Sasson Y, Gevorkyan-Airapetov L, Lahav-Mankovski N, Margulies D, Radzimanowski J, Opatowsky Y Structure. 2015 Nov 3;23(11):1989-2000. doi: 10.1016/j.str.2015.08.009. Epub 2015, Sep 10. PMID:26365803^[4]

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

References

↑ Guo S, Bao S. srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization. J Biol Chem. 2010 Nov 5;285(45):35133-41. doi: 10.1074/jbc.M110.153429. Epub 2010, Sep 1. PMID:20810653 doi:10.1074/jbc.M110.153429
↑ Mason FM, Heimsath EG, Higgs HN, Soderling SH. Bi-modal regulation of a formin by srGAP2. J Biol Chem. 2011 Feb 25;286(8):6577-86. doi: 10.1074/jbc.M110.190397. Epub 2010 , Dec 9. PMID:21148482 doi:10.1074/jbc.M110.190397
↑ Charrier C, Joshi K, Coutinho-Budd J, Kim JE, Lambert N, de Marchena J, Jin WL, Vanderhaeghen P, Ghosh A, Sassa T, Polleux F. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell. 2012 May 11;149(4):923-35. doi: 10.1016/j.cell.2012.03.034. Epub 2012 May, 3. PMID:22559944 doi:10.1016/j.cell.2012.03.034
↑ Guez-Haddad J, Sporny M, Sasson Y, Gevorkyan-Airapetov L, Lahav-Mankovski N, Margulies D, Radzimanowski J, Opatowsky Y. The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism. Structure. 2015 Nov 3;23(11):1989-2000. doi: 10.1016/j.str.2015.08.009. Epub 2015, Sep 10. PMID:26365803 doi:http://dx.doi.org/10.1016/j.str.2015.08.009

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rtt"

@@ Line 1: / Line 1: @@
 ==Cyrstal structure of SLIT-ROBO Rho GTPase-activating protein 2 fragment==
 <StructureSection load='4rtt' size='340' side='right' caption='[[4rtt]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rtt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RTT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RTT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rtt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RTT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RTT FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rug|4rug]]</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=4rtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rtt OCA], [http://pdbe.org/4rtt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rtt RCSB], [http://www.ebi.ac.uk/pdbsum/4rtt PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRGAP2, ARHGAP34, FNBP2, KIAA0456, SRGAP2A ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rtt OCA], [http://pdbe.org/4rtt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rtt RCSB], [http://www.ebi.ac.uk/pdbsum/4rtt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rtt ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Guez-Hadad, J]]
 [[Category: Opatowsky, Y]]

4rtt

From Proteopedia

Revision as of 09:09, 22 November 2017

Cyrstal structure of SLIT-ROBO Rho GTPase-activating protein 2 fragment

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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