6tgb: Difference between revisions
New page: '''Unreleased structure''' The entry 6tgb is ON HOLD Authors: Description: Category: Unreleased Structures |
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==CryoEM structure of the binary DOCK2-ELMO1 complex== | |||
<StructureSection load='6tgb' size='340' side='right'caption='[[6tgb]], [[Resolution|resolution]] 5.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6tgb]] is a 3 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=6TGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TGB 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]] 5.5Å</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=6tgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tgb OCA], [https://pdbe.org/6tgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tgb RCSB], [https://www.ebi.ac.uk/pdbsum/6tgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tgb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DOCK2_HUMAN DOCK2_HUMAN] Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2.<ref>PMID:21613211</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6tgb" 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]] | |||
== 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]] | |||
Latest revision as of 13:18, 22 May 2024
CryoEM structure of the binary DOCK2-ELMO1 complexCryoEM structure of the binary DOCK2-ELMO1 complex
Structural highlights
FunctionDOCK2_HUMAN Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2.[1] Publication Abstract from PubMedDOCK (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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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