6TGB

CryoEM structure of the binary DOCK2-ELMO1 complex

Summary for 6TGB

• Entry DOI: 10.2210/pdb6tgb/pdb
• EMDB information: 10497
• Descriptor: Dedicator of cytokinesis protein 2, Engulfment and cell motility protein 1 (2 entities in total)
• Functional Keywords: guanine nucleotide exchange factor, cytoskeleton, actin, cryoem, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 475696.36

Authors

Chang, L.,Yang, J.,Chang, J.H.,Zhang, Z.,Boland, A.,McLaughlin, S.H.,Abu-Thuraia, A.,Killoran, R.C.,Smith, M.J.,Cote, J.F.,Barford, D. (deposition date: 2019-11-15, release date: 2020-07-29, Last modification date: 2024-05-22)

Primary citation

Chang, L.,Yang, J.,Jo, C.H.,Boland, A.,Zhang, Z.,McLaughlin, S.H.,Abu-Thuraia, A.,Killoran, R.C.,Smith, M.J.,Cote, J.F.,Barford, D.
Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state.
Nat Commun, 11:3464-3464, 2020

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) 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.

PubMed: 32651375
DOI: 10.1038/s41467-020-17271-9

Experimental method

ELECTRON MICROSCOPY (5.5 Å)