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6tgc

From Proteopedia

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Current revision

CryoEM structure of the ternary DOCK2-ELMO1-RAC1 complex.

Structural highlights

6tgc is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kulkarni K, Yang J, Zhang Z, Barford D. Multiple Factors Confer Specific Cdc42 and Rac Protein Activation by Dedicator of Cytokinesis (DOCK) Nucleotide Exchange Factors. J Biol Chem. 2011 Jul 15;286(28):25341-51. Epub 2011 May 24. PMID:21613211 doi:10.1074/jbc.M111.236455
↑ Chang L, Yang J, Jo CH, Boland A, Zhang Z, McLaughlin SH, Abu-Thuraia A, Killoran RC, Smith MJ, Côté JF, Barford D. Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state. Nat Commun. 2020 Jul 10;11(1):3464. PMID:32651375 doi:10.1038/s41467-020-17271-9

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6tgc"

@@ Line 4: / Line 4: @@
 == 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='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>
+</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 ==

6tgc

From Proteopedia

Current revision

CryoEM structure of the ternary DOCK2-ELMO1-RAC1 complex.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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