4FID

Crystal structure of a heterotrimeric G-Protein subunit from entamoeba histolytica, EHG-ALPHA-1

Summary for 4FID

• Entry DOI: 10.2210/pdb4fid/pdb
• Descriptor: G protein alpha subunit, GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: ras-like domain, all-helical domain, gtp binding, nucleotide binding, signaling protein, transducer, lipoprotein, reductive methylation
• Biological source: Entamoeba histolytica
• Total number of polymer chains: 2
• Total formula weight: 78178.31

Authors

Bosch, D.E.,Kimple, A.J.,Muller, R.E.,Gigure, P.M.,Willard, F.S.,Machius, M.,Temple, B.R.,Siderovski, D.P. (deposition date: 2012-06-08, release date: 2012-11-28, Last modification date: 2025-03-26)

Primary citation

Bosch, D.E.,Kimple, A.J.,Muller, R.E.,Giguere, P.M.,Machius, M.,Willard, F.S.,Temple, B.R.,Siderovski, D.P.
Heterotrimeric G-protein Signaling Is Critical to Pathogenic Processes in Entamoeba histolytica.
Plos Pathog., 8:e1003040-e1003040, 2012

PubMed 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.

PubMed: 23166501
DOI: 10.1371/journal.ppat.1003040

Experimental method

X-RAY DIFFRACTION (2.62 Å)