Entamoeba histolytica Rho1 regulates actin polymerization through a divergent, Diaphanous-related formin

Dustin E Bosch; Bing Yang; David P Siderovski; Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

doi:10.1021/bi300954g

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Entamoeba histolytica Rho1 regulates actin polymerization through a divergent, Diaphanous-related formin

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Entamoeba histolytica Rho1 regulates actin polymerization through a divergent, Diaphanous-related formin

Dustin E Bosch, Bing Yang, David P Siderovski and Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Biochemistry (Easton), Vol.51(44), pp.8791-8801

11/06/2012

DOI: 10.1021/bi300954g

PMCID: PMC3491106

PMID: 23050667

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https://www.ncbi.nlm.nih.gov/pmc/articles/3491106View

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Abstract

Entamoeba histolytica requires a dynamic actin cytoskeleton for intestinal and systemic pathogenicity. Diaphanous-related formins represent an important family of actin regulators that are activated by Rho GTPases. The E. histolytica genome encodes a large family of Rho GTPases and three diaphanous-related formins, of which EhFormin1 is known to regulate mitosis and cytokinesis in trophozoites. We demonstrate that EhFormin1 modulates actin polymerization through its formin homology 2 (FH2) domain. Despite a highly divergent diaphanous autoinhibitory domain, EhFormin1 is autoinhibited by an N- and C-terminal intramolecular interaction, but activated upon binding of EhRho1 to the N-terminal domain tandem. A crystal structure of the EhRho1·GTPγS/EhFormin1 complex illustrates an EhFormin1 conformation that diverges from mammalian mDia1 and lacks a secondary interaction with a Rho insert helix. The structural model also highlights residues required for specific recognition of the EhRho1 GTPase and suggests that the molecular mechanisms of EhFormin1 autoinhibition and activation differ from mammalian homologs.

actin polymerization

guanine nucleotide binding protein

Details

Title: Subtitle: Entamoeba histolytica Rho1 regulates actin polymerization through a divergent, Diaphanous-related formin
Creators: Dustin E Bosch - University of North Carolina at Chapel Hill
Bing Yang - University of North Carolina at Chapel Hill
David P Siderovski - West Virginia University
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Resource Type: Journal article
Publication Details: Biochemistry (Easton), Vol.51(44), pp.8791-8801
DOI: 10.1021/bi300954g
PMID: 23050667
PMCID: PMC3491106
NLM abbreviation: Biochemistry
ISSN: 0006-2960
eISSN: 1520-4995
Grant note: R01 GM082892 || GM / National Institute of General Medical Sciences : NIGMS
Language: English
Date published: 11/06/2012
Academic Unit: Pathology
Record Identifier: 9984200019902771

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