PDBsum entry 4gou

Signaling protein

PDB id: 4gou

Contents

Protein chain

507 a.a.

Waters ×216

PDB id:

4gou

Name:

Signaling protein

Title:

Crystal structure of an rgs-rhogef from entamoeba histolytica

Structure:

Ehrgs-rhogef. Chain: a. Engineered: yes

Source:

Entamoeba histolytica. Organism_taxid: 5759. Strain: hm-1:imss. Gene: ehi_010670, ehrgs-rhogef. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.185 R-free: 0.236

Authors:

D.E.Bosch,A.J.Kimple,R.E.Muller,F.S.Willard,M.Machius,D.P.Siderovski

Key ref:

D.E.Bosch et al. (2013). Structural determinants of RGS-RhoGEF signaling critical to Entamoeba histolytica pathogenesis. Structure, 21, 65-75. PubMed id: 23260656

Date:

20-Aug-12 Release date: 09-Jan-13

Protein chain

C4LYV4  (C4LYV4_ENTHI) -  Regulator of g protein signaling domain containing protein from Entamoeba histolytica (strain ATCC 30459 / HM-1:IMSS / ABRM)

Seq: 519 a.a.

Struc: 507 a.a.

Structure 21:65-75 (2013)

PubMed id: 23260656

Structural determinants of RGS-RhoGEF signaling critical to Entamoeba histolytica pathogenesis.

D.E.Bosch, A.J.Kimple, A.J.Manning, R.E.Muller, F.S.Willard, M.Machius, S.L.Rogers, D.P.Siderovski.

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.