View source for 8zjl


==Structure of DOCK5/ELMO1/Rac1 core (RhoG/DOCK5/ELMO1/Rac1 dataset, class 4)==
<StructureSection load='8zjl' size='340' side='right'caption='[[8zjl]], [[Resolution|resolution]] 4.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zjl]] 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=8ZJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZJL 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]] 4.31&#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=8zjl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zjl OCA], [https://pdbe.org/8zjl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zjl RCSB], [https://www.ebi.ac.uk/pdbsum/8zjl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zjl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ELMO1_HUMAN ELMO1_HUMAN] Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in assocation with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1.<ref>PMID:11595183</ref> <ref>PMID:12134158</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The dedicator of cytokinesis (DOCK)/engulfment and cell motility (ELMO) complex serves as a guanine nucleotide exchange factor (GEF) for the GTPase Rac. RhoG, another GTPase, activates the ELMO-DOCK-Rac pathway during engulfment and migration. Recent cryo-EM structures of the DOCK2/ELMO1 and DOCK2/ELMO1/Rac1 complexes have identified closed and open conformations that are key to understanding the autoinhibition mechanism. Nevertheless, the structural details of RhoG-mediated activation of the DOCK/ELMO complex remain elusive. Herein, we present cryo-EM structures of DOCK5/ELMO1 alone and in complex with RhoG and Rac1. The DOCK5/ELMO1 structure exhibits a closed conformation similar to that of DOCK2/ELMO1, suggesting a shared regulatory mechanism of the autoinhibitory state across DOCK-A/B subfamilies (DOCK1-5). Conversely, the RhoG/DOCK5/ELMO1/Rac1 complex adopts an open conformation that differs from that of the DOCK2/ELMO1/Rac1 complex, with RhoG binding to both ELMO1 and DOCK5. The alignment of the DOCK5 phosphatidylinositol (3,4,5)-trisphosphate binding site with the RhoG C-terminal lipidation site suggests simultaneous binding of RhoG and DOCK5/ELMO1 to the plasma membrane. Structural comparison of the apo and RhoG-bound states revealed that RhoG facilitates a closed-to-open state conformational change of DOCK5/ELMO1. Biochemical and surface plasmon resonance (SPR) assays confirm that RhoG enhances the Rac GEF activity of DOCK5/ELMO1 and increases its binding affinity for Rac1. Further analysis of structural variability underscored the conformational flexibility of the DOCK5/ELMO1/Rac1 complex core, potentially facilitating the proximity of the DOCK5 GEF domain to the plasma membrane. These findings elucidate the structural mechanism underlying the RhoG-induced allosteric activation and membrane binding of the DOCK/ELMO complex.

RhoG facilitates a conformational transition in the guanine nucleotide exchange factor complex DOCK5/ELMO1 to an open state.,Kukimoto-Niino M, Katsura K, Ishizuka-Katsura Y, Mishima-Tsumagari C, Yonemochi M, Inoue M, Nakagawa R, Kaushik R, Zhang KYJ, Shirouzu M J Biol Chem. 2024 Jun 8;300(7):107459. doi: 10.1016/j.jbc.2024.107459. PMID:38857861<ref>PMID:38857861</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zjl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Inoue M]]
[[Category: Ishizuka-Katsura Y]]
[[Category: Katsura K]]
[[Category: Kaushik R]]
[[Category: Kukimoto-Niino M]]
[[Category: Mishima-Tsumagari C]]
[[Category: Nakagawa R]]
[[Category: Shirouzu M]]
[[Category: Yonemochi M]]
[[Category: Zhang KYJ]]