6UKA

Crystal structure of RHOG and ELMO complex

Summary for 6UKA

• Entry DOI: 10.2210/pdb6uka/pdb
• Descriptor: Rho-related GTP-binding protein RhoG, Engulfment and cell motility protein 2, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• Functional Keywords: rhog, elmo, rbd, complex, cell adhesion, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 30913.24

Authors

Jo, C.H.,Killoran, R.C.,Smith, M.J. (deposition date: 2019-10-04, release date: 2020-08-12, Last modification date: 2023-10-11)

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

X-RAY DIFFRACTION (2.4 Å)