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-Structure paper
Title | Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 3464, Year 2020 |
Publish date | Jul 10, 2020 |
Authors | Leifu Chang / Jing Yang / Chang Hwa Jo / Andreas Boland / Ziguo Zhang / Stephen H McLaughlin / Afnan Abu-Thuraia / Ryan C Killoran / Matthew J Smith / Jean-Francois Côté / David Barford / |
PubMed Abstract | 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) ...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) and membrane-associated (DOCK) 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) 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 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, 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. |
External links | Nat Commun / PubMed:32651375 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.4 - 5.5 Å |
Structure data | EMDB-10497, PDB-6tgb: EMDB-10498: CryoEM structure of the ternary DOCK2-ELMO1-RAC1 complex PDB-6uka: |
Chemicals | ChemComp-GNP: ChemComp-MG: ChemComp-HOH: |
Source |
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Keywords | SIGNALING PROTEIN / guanine nucleotide exchange factor / cytoskeleton / actin / cryoEM / RHOG / ELMO / RBD / complex / CELL ADHESION |