The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

Ruan, Jiapeng; Mouveaux, Thomas; Light, Samuel H.; Minasov, George; Anderson, Wayne F.; Tomavo, Stanislas; Ngô, Huân M.

doi:10.1107/S1399004714026479

The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

Journal Article · Sat Feb 28 23:00:00 EST 2015 · Acta Crystallographica. Section D: Biological Crystallography (Online)

DOI:https://doi.org/10.1107/S1399004714026479· OSTI ID:1172406

Ruan, Jiapeng ^[1]; Mouveaux, Thomas ^[2]; Light, Samuel H. ^[1]; Minasov, George ^[1]; Anderson, Wayne F. ^[1]; Tomavo, Stanislas ^[3]; Ngô, Huân M. ^[4]

Northwestern Univ., Chicago, IL (United States). Center for Structural Genomics of Infectious Diseases
Univ. Lille Nord de France (France). Inst. Pasteur de Lille, Center for Infection and Immunity of Lille
Univ. Lille Nord de France (France). Inst. Pasteur de Lille, Center for Infection and Immunity of Lille
Northwestern Univ., Chicago, IL (United States). Center for Structural Genomics of Infectious Diseases; BrainMicro LLC, New Haven, CT (United States)

In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein inToxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated n vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Lastly, enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); France National Agency for Research

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1172406

Alternate ID(s):: OSTI ID: 22347716

Journal Information:: Acta Crystallographica. Section D: Biological Crystallography (Online), Journal Name: Acta Crystallographica. Section D: Biological Crystallography (Online) Journal Issue: 3 Vol. 71; ISSN 1399-0047; ISSN ABCRE6

Publisher:: International Union of CrystallographyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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