View source for 6gvc


==Structure of ArhGAP12 bound to G-Actin==
<StructureSection load='6gvc' size='340' side='right'caption='[[6gvc]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gvc]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GVC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LAB:LATRUNCULIN+B'>LAB</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">Arhgap12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6gvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gvc OCA], [http://pdbe.org/6gvc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gvc RCSB], [http://www.ebi.ac.uk/pdbsum/6gvc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gvc ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[http://www.uniprot.org/uniprot/RHG12_MOUSE RHG12_MOUSE]] GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RPEL proteins, which contain the G-actin-binding RPEL motif, coordinate cytoskeletal processes with actin dynamics. We show that the ArhGAP12- and ArhGAP32-family GTPase-activating proteins (GAPs) are RPEL proteins. We determine the structure of the ArhGAP12/G-actin complex, and show that G-actin contacts the RPEL motif and GAP domain sequences. G-actin inhibits ArhGAP12 GAP activity, and this requires the G-actin contacts identified in the structure. In B16 melanoma cells, ArhGAP12 suppresses basal Rac and Cdc42 activity, F-actin assembly, invadopodia formation and experimental metastasis. In this setting, ArhGAP12 mutants defective for G-actin binding exhibit more effective downregulation of Rac GTP loading following HGF stimulation and enhanced inhibition of Rac-dependent processes, including invadopodia formation. Potentiation or disruption of the G-actin/ArhGAP12 interaction, by treatment with the actin-binding drugs latrunculin B or cytochalasin D, has corresponding effects on Rac GTP loading. The interaction of G-actin with RPEL-family rhoGAPs thus provides a negative feedback loop that couples Rac activity to actin dynamics.

RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability.,Diring J, Mouilleron S, McDonald NQ, Treisman R Nat Cell Biol. 2019 Jul;21(7):845-855. doi: 10.1038/s41556-019-0337-y. Epub 2019 , Jun 17. PMID:31209295<ref>PMID:31209295</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gvc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Oryctolagus cuniculus]]
[[Category: Diring, J]]
[[Category: Mouilleron, S]]
[[Category: Treisman, R]]
[[Category: Actin]]
[[Category: Gap]]
[[Category: Hydrolase]]
[[Category: Rac]]