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PDBsum entry 4gou
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Signaling protein
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PDB id
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4gou
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References listed in PDB file
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Key reference
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Title
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Structural determinants of rgs-Rhogef signaling critical to entamoeba histolytica pathogenesis.
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Authors
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D.E.Bosch,
A.J.Kimple,
A.J.Manning,
R.E.Muller,
F.S.Willard,
M.Machius,
S.L.Rogers,
D.P.Siderovski.
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Ref.
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Structure, 2013,
21,
65-75.
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PubMed id
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Abstract
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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.
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