| Structural highlights
Function
RHOG_HUMAN Required for the formation of membrane ruffles during macropinocytosis. Plays a role in cell migration and is required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB and ARHGEF26/SGEF, which induces cytoskeleton rearrangements and promotes bacterial entry.[1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ellerbroek SM, Wennerberg K, Arthur WT, Dunty JM, Bowman DR, DeMali KA, Der C, Burridge K. SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis. Mol Biol Cell. 2004 Jul;15(7):3309-19. Epub 2004 May 7. PMID:15133129 doi:http://dx.doi.org/10.1091/mbc.E04-02-0146
- ↑ Patel JC, Galan JE. Differential activation and function of Rho GTPases during Salmonella-host cell interactions. J Cell Biol. 2006 Nov 6;175(3):453-63. doi: 10.1083/jcb.200605144. Epub 2006 Oct , 30. PMID:17074883 doi:http://dx.doi.org/10.1083/jcb.200605144
- ↑ van Buul JD, Allingham MJ, Samson T, Meller J, Boulter E, Garcia-Mata R, Burridge K. RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration. J Cell Biol. 2007 Sep 24;178(7):1279-93. Epub 2007 Sep 17. PMID:17875742 doi:10.1083/jcb.200612053
- ↑ Hiramoto-Yamaki N, Takeuchi S, Ueda S, Harada K, Fujimoto S, Negishi M, Katoh H. Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. J Cell Biol. 2010 Aug 9;190(3):461-77. doi: 10.1083/jcb.201005141. Epub 2010 Aug , 2. PMID:20679435 doi:10.1083/jcb.201005141
- ↑ 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
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