View source for 6tgc


==CryoEM structure of the ternary DOCK2-ELMO1-RAC1 complex.==
<StructureSection load='6tgc' size='340' side='right'caption='[[6tgc]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tgc]] is a 6 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=6TGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TGC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1&#8491;</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=6tgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tgc OCA], [https://pdbe.org/6tgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tgc RCSB], [https://www.ebi.ac.uk/pdbsum/6tgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tgc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAC1_HUMAN RAC1_HUMAN] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref>   Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DOCK (dedicator of cytokinesis) proteins are multidomain guanine nucleotide exchange factors (GEFs) for RHO GTPases that regulate intracellular actin dynamics. DOCK proteins share catalytic (DOCK(DHR2)) and membrane-associated (DOCK(DHR1)) domains. The structurally-related DOCK1 and DOCK2 GEFs are specific for RAC, and require ELMO (engulfment and cell motility) proteins for function. The N-terminal RAS-binding domain (RBD) of ELMO (ELMO(RBD)) interacts with RHOG to modulate DOCK1/2 activity. Here, we determine the cryo-EM structures of DOCK2-ELMO1 alone, and as a ternary complex with RAC1, together with the crystal structure of a RHOG-ELMO2(RBD) complex. The binary DOCK2-ELMO1 complex adopts a closed, auto-inhibited conformation. Relief of auto-inhibition to an active, open state, due to a conformational change of the ELMO1 subunit, exposes binding sites for RAC1 on DOCK2(DHR2), and RHOG and BAI GPCRs on ELMO1. Our structure explains how up-stream effectors, including DOCK2 and ELMO1 phosphorylation, destabilise the auto-inhibited state to promote an active GEF.

Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state.,Chang L, Yang J, Jo CH, Boland A, Zhang Z, McLaughlin SH, Abu-Thuraia A, Killoran RC, Smith MJ, Cote JF, Barford D Nat Commun. 2020 Jul 10;11(1):3464. doi: 10.1038/s41467-020-17271-9. PMID:32651375<ref>PMID:32651375</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6tgc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dedicator of cytokinesis protein 3D structures|Dedicator of cytokinesis protein 3D structures]]
*[[Engulfment and cell motility protein 1|Engulfment and cell motility protein 1]]
*[[Rac 3D structures|Rac 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abu-Thuraia A]]
[[Category: Barford D]]
[[Category: Boland A]]
[[Category: Chang JH]]
[[Category: Chang L]]
[[Category: Cote JF]]
[[Category: Killoran RC]]
[[Category: McLaughlin SH]]
[[Category: Smith MJ]]
[[Category: Yang J]]
[[Category: Zhang Z]]