Evidence map›Paper›PMID 23260656›Full record

ArticleStructure (London, England : 1993)2013

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

Dustin E Bosch, Adam J Kimple, Alyssa J Manning, Robin E Muller, Francis S Willard, Mischa Machius, Stephen L Rogers, David P Siderovski

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Regulation of virulence of Entamoeba histolytica.Annual review of microbiology · 2014
    Review
  5. G protein signaling in the parasite Entamoeba histolytica.Experimental & molecular medicine · 2013
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Dustin E BoschDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Adam J KimpleDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Alyssa J ManningDepartment of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Robin E MullerDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Francis S WillardDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Mischa MachiusDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Stephen L RogersDepartment of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
David P SiderovskiDepartment of Physiology and Pharmacology, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center, Morgantown, WV 26506, USA. Electronic address: dpsiderovski@hsc.wvu.edu.
University of North Carolina at Chapel Hill · USWest Virginia University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008719 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DARVILLE, TONI, DESHMUKH, MOHANISH P · 1999 to 2023
$15.1M
Structural Determinants of Heterotrimeric G-protein Nucleotide CyclingR01GM082892 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SIDEROVSKI, DAVID P. · 2008 to 2011
$924k
Towards small molecule modulators of RGS proteinsF30MH074266 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIMPLE, ADAM J · 2006 to 2011
$162k
Elucidating a G-protein signaling pathway in E. histolytica amoebic colitisF30DK091978 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOSCH, DUSTIN E · 2011 to 2013
$105k
NIDDK NIH HHS DK091978NIDDK NIH HHS F30 DK091978NIGMS NIH HHS GM082892NIGMS NIH HHS R01 GM082892NIGMS NIH HHS T32 GM008719NIMH NIH HHS F30 MH074266NIMH NIH HHS MH074266
6 · The paper itself

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.

Indexed as

Signal TransductionAmino Acid SubstitutionAnimalsBinding SitesCell AdhesionCell LineCell ShapeCell SurvivalChemotaxisCrystallography, X-RayDrosophila melanogasterEntamoeba histolyticaGTP-Binding Protein alpha SubunitsGuanine Nucleotide Exchange FactorsGuanosine TriphosphateHost-Parasite InteractionsGTP-Binding Protein alpha SubunitsGuanine Nucleotide Exchange FactorsGuanosine TriphosphateProtozoan ProteinsRho Guanine Nucleotide Exchange Factors

Identifiers

PMID23260656
PMCPMC3545058
OpenAlexW2081606766

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.