4GOU

Crystal structure of an RGS-RhoGEF from Entamoeba histolytica

Summary for 4GOU

• Entry DOI: 10.2210/pdb4gou/pdb
• Related: 4FID
• Descriptor: EhRGS-RhoGEF (2 entities in total)
• Functional Keywords: rgs domain, dh domain, ph domain, rho guanine nucleotide exchange factor, signaling protein, gtpase accelerating protein, phospholipid binding, heterotrimeric g protein effector, ehgalpha1
• Biological source: Entamoeba histolytica
• Total number of polymer chains: 1
• Total formula weight: 60454.88

Authors

Bosch, D.E.,Kimple, A.J.,Muller, R.E.,Willard, F.S.,Machius, M.,Siderovski, D.P. (deposition date: 2012-08-20, release date: 2013-01-09, Last modification date: 2024-10-09)

Primary citation

Bosch, D.E.,Kimple, A.J.,Manning, A.J.,Muller, R.E.,Willard, F.S.,Machius, M.,Rogers, S.L.,Siderovski, D.P.
Structural Determinants of RGS-RhoGEF Signaling Critical to Entamoeba histolytica Pathogenesis.
Structure, 21:65-75, 2013

PubMed Abstract: G protein signaling pathways, as key components of physiologic responsiveness and timing, are frequent targets for pharmacologic intervention. Here, we identify an effector for heterotrimeric G protein α subunit (EhGα1) signaling from Entamoeba histolytica, the causative agent of amoebic colitis. EhGα1 interacts with this effector and guanosine triphosphatase-accelerating protein, EhRGS-RhoGEF, in a nucleotide state-selective fashion. Coexpression of EhRGS-RhoGEF with constitutively active EhGα1 and EhRacC leads to Rac-dependent spreading in Drosophila S2 cells. EhRGS-RhoGEF overexpression in E. histolytica trophozoites leads to reduced migration toward serum and lower cysteine protease activity, as well as reduced attachment to, and killing of, host cells. A 2.3 Å crystal structure of the full-length EhRGS-RhoGEF reveals a putative inhibitory helix engaging the Dbl homology domain Rho-binding surface and the pleckstrin homology domain. Mutational analysis of the EhGα1/EhRGS-RhoGEF interface confirms a canonical "regulator of G protein signaling" domain rather than a RhoGEF-RGS ("rgRGS") domain, suggesting a convergent evolution toward heterotrimeric and small G protein cross-talk.

PubMed: 23260656
DOI: 10.1016/j.str.2012.11.012

Experimental method

X-RAY DIFFRACTION (2.3 Å)