5i6j

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of SRGAP2 F-BARx

Structural highlights

5i6j is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
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

In the development of the human brain, human-specific genes are considered to play key roles, conferring its unique advantages and vulnerabilities. At the time of Homo lineage divergence from Australopithecus, SRGAP2C gradually emerged through a process of serial duplications and mutagenesis from ancestral SRGAP2A (3.4-2.4 Ma). Remarkably, ectopic expression of SRGAP2C endows cultured mouse brain cells, with human-like characteristics, specifically, increased dendritic spine length and density. To understand the molecular mechanisms underlying this change in neuronal morphology, we determined the structure of SRGAP2A and studied the interplay between SRGAP2A and SRGAP2C. We found that: 1) SRGAP2A homo-dimerizes through a large interface that includes an F-BAR domain, a newly identified F-BAR extension (Fx), and RhoGAP-SH3 domains. 2) SRGAP2A has an unusual inverse geometry, enabling associations with lamellipodia and dendritic spine heads in vivo, and scaffolding of membrane protrusions in cell culture. 3) As a result of the initial partial duplication event ( approximately 3.4 Ma), SRGAP2C carries a defective Fx-domain that severely compromises its solubility and membrane-scaffolding ability. Consistently, SRGAP2A:SRAGP2C hetero-dimers form, but are insoluble, inhibiting SRGAP2A activity. 4) Inactivation of SRGAP2A is sensitive to the level of hetero-dimerization with SRGAP2C. 5) The primal form of SRGAP2C (P-SRGAP2C, existing between approximately 3.4 and 2.4 Ma) is less effective in hetero-dimerizing with SRGAP2A than the modern SRGAP2C, which carries several substitutions (from approximately 2.4 Ma). Thus, the genetic mutagenesis phase contributed to modulation of SRGAP2A's inhibition of neuronal expansion, by introducing and improving the formation of inactive SRGAP2A:SRGAP2C hetero-dimers, indicating a stepwise involvement of SRGAP2C in human evolutionary history.

Structural History of Human SRGAP2 Proteins.,Sporny M, Guez-Haddad J, Kreusch A, Shakartzi S, Neznansky A, Cross A, Isupov MN, Qualmann B, Kessels MM, Opatowsky Y Mol Biol Evol. 2017 Feb 21. doi: 10.1093/molbev/msx094. PMID:28333212^[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
↑ Sporny M, Guez-Haddad J, Kreusch A, Shakartzi S, Neznansky A, Cross A, Isupov MN, Qualmann B, Kessels MM, Opatowsky Y. Structural History of Human SRGAP2 Proteins. Mol Biol Evol. 2017 Feb 21. doi: 10.1093/molbev/msx094. PMID:28333212 doi:http://dx.doi.org/10.1093/molbev/msx094

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5i6j"

@@ Line 3: / Line 3: @@
 <StructureSection load='5i6j' size='340' side='right'caption='[[5i6j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5i6j]] is a 1 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=5I6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I6J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5i6j]] is a 1 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=5I6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I6J FirstGlance]. <br>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</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=5i6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i6j OCA], [http://pdbe.org/5i6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i6j RCSB], [http://www.ebi.ac.uk/pdbsum/5i6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i6j 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=5i6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i6j OCA], [https://pdbe.org/5i6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i6j RCSB], [https://www.ebi.ac.uk/pdbsum/5i6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i6j ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/SRGP2_HUMAN 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).
+[https://www.uniprot.org/uniprot/SRGP2_HUMAN 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 ==
-[[http://www.uniprot.org/uniprot/SRGP2_HUMAN 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.<ref>PMID:20810653</ref> <ref>PMID:21148482</ref> <ref>PMID:22559944</ref>
+[https://www.uniprot.org/uniprot/SRGP2_HUMAN 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.<ref>PMID:20810653</ref> <ref>PMID:21148482</ref> <ref>PMID:22559944</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[Rho GTPase activating protein|Rho GTPase activating protein]]
+*[[Rho GTPase activating protein 3D structures|Rho GTPase activating protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Guez-Haddad, J]]
+[[Category: Guez-Haddad J]]
-[[Category: Isupov, M N]]
+[[Category: Isupov MN]]
-[[Category: Opatowsky, Y]]
+[[Category: Opatowsky Y]]
-[[Category: Sporny, M]]
+[[Category: Sporny M]]
-[[Category: F-bar]]
-[[Category: Fx]]
-[[Category: Signaling protein]]
-[[Category: Srgap2]]

5i6j

From Proteopedia

Current revision

Crystal Structure of SRGAP2 F-BARx

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox