8zj2
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of the RhoG/DOCK5/ELMO1/Rac1 complex== | |
| + | <StructureSection load='8zj2' size='340' side='right'caption='[[8zj2]], [[Resolution|resolution]] 4.66Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8zj2]] is a 7 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=8ZJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZJ2 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]] 4.66Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=8zj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zj2 OCA], [https://pdbe.org/8zj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zj2 RCSB], [https://www.ebi.ac.uk/pdbsum/8zj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zj2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DOCK5_HUMAN DOCK5_HUMAN] Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF proteins activate small GTPases by exchanging bound GDP for free GTP (By similarity). Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829).[UniProtKB:B2RY04]<ref>PMID:19004829</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8zj2" 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]] | ||
Current revision
Cryo-EM structure of the RhoG/DOCK5/ELMO1/Rac1 complex
| |||||||||||
