4gou
From Proteopedia
Crystal structure of an RGS-RhoGEF from Entamoeba histolytica
Structural highlights
FunctionPublication Abstract from PubMedG 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 alpha subunit (EhGalpha1) signaling from Entamoeba histolytica, the causative agent of amoebic colitis. EhGalpha1 interacts with this effector and guanosine triphosphatase-accelerating protein, EhRGS-RhoGEF, in a nucleotide state-selective fashion. Coexpression of EhRGS-RhoGEF with constitutively active EhGalpha1 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 A 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 EhGalpha1/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. Structural Determinants of RGS-RhoGEF Signaling Critical to Entamoeba histolytica Pathogenesis.,Bosch DE, Kimple AJ, Manning AJ, Muller RE, Willard FS, Machius M, Rogers SL, Siderovski DP Structure. 2012 Dec 19. pii: S0969-2126(12)00427-3. doi:, 10.1016/j.str.2012.11.012. PMID:23260656[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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