PDBsum entry 4fid

Signaling protein

PDB id: 4fid

Contents

Protein chains

318 a.a.

Ligands

GDP ×2

Waters ×39

PDB id:

4fid

Name:

Signaling protein

Title:

Crystal structure of a heterotrimeric g-protein subunit from entamoeba histolytica, ehg-alpha-1

Structure:

G protein alpha subunit. Chain: a, b. Fragment: unp residues 22-358. Engineered: yes

Source:

Entamoeba histolytica. Organism_taxid: 5759. Strain: hm1:imss. Gene: ehg-alpha-1, ehi_140350. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.62Å R-factor: 0.193 R-free: 0.258

Authors:

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

Key ref:

D.E.Bosch et al. (2012). Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica. Plos Pathog, 8, e1003040. PubMed id: 23166501

Date:

08-Jun-12 Release date: 28-Nov-12

Protein chains

C4M483  (C4M483_ENTHI) -  G protein alpha subunit, putative from Entamoeba histolytica (strain ATCC 30459 / HM-1:IMSS / ABRM)

Seq: 358 a.a.

Struc: 318 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Plos Pathog 8:e1003040 (2012)

PubMed id: 23166501

Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.

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

ABSTRACT

Heterotrimeric G-protein signaling pathways are vital components of physiology, and many are amenable to pharmacologic manipulation. Here, we identify functional heterotrimeric G-protein subunits in Entamoeba histolytica, the causative agent of amoebic colitis. The E. histolytica Gα subunit EhGα1 exhibits conventional nucleotide cycling properties and is seen to interact with EhGβγ dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhGα1 highlights unique features and classification outside of conventional mammalian Gα subfamilies. E. histolytica trophozoites overexpressing wildtype EhGα1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhGα1-overexpressing trophozoites also display enhanced transmigration across a Matrigel barrier, an effect that may result from altered baseline migration. Inducible expression of a dominant negative EhGα1 variant engenders the converse phenotypes. Transcriptomic studies reveal that modulation of pathogenesis-related trophozoite behaviors by perturbed heterotrimeric G-protein expression includes transcriptional regulation of virulence factors and altered trafficking of cysteine proteases. Collectively, our studies suggest that E. histolytica possesses a divergent heterotrimeric G-protein signaling axis that modulates key aspects of cellular processes related to the pathogenesis of this infectious organism.