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

Abstract

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 potentialmore » lead in the design of drugs against Toxoplasma brain cysts.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [3];  [4]
+ Show Author Affiliations
  1. Northwestern Univ., Chicago, IL (United States). Center for Structural Genomics of Infectious Diseases
  2. Univ. Lille Nord de France (France). Inst. Pasteur de Lille, Center for Infection and Immunity of Lille
  3. Univ. Lille Nord de France (France). Inst. Pasteur de Lille, Center for Infection and Immunity of Lille
  4. Northwestern Univ., Chicago, IL (United States). Center for Structural Genomics of Infectious Diseases; BrainMicro LLC, New Haven, CT (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); France National Agency for Research
OSTI Identifier:
1172406
Grant/Contract Number:  
AC02-06CH11357; HHSN272200700058C; HHSN272201200026C; 085P1000817; 3RO1DAO13141- 08S1
Resource Type:
Accepted Manuscript
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography (Online)
Additional Journal Information:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography (Online); Journal Volume: 71; Journal Issue: 3; Journal ID: ISSN 1399-0047
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; moonlighting protein; brain parasite; central nervous system; chronic infection; differentiation

Citation Formats

Ruan, Jiapeng, Mouveaux, Thomas, Light, Samuel H., Minasov, George, Anderson, Wayne F., Tomavo, Stanislas, and Ngô, Huân M. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions. United States: N. p., 2015. Web. doi:10.1107/S1399004714026479.
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Ruan, Jiapeng, Mouveaux, Thomas, Light, Samuel H., Minasov, George, Anderson, Wayne F., Tomavo, Stanislas, & Ngô, Huân M. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions. United States. https://doi.org/10.1107/S1399004714026479
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Ruan, Jiapeng, Mouveaux, Thomas, Light, Samuel H., Minasov, George, Anderson, Wayne F., Tomavo, Stanislas, and Ngô, Huân M. Sun . "The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions". United States. https://doi.org/10.1107/S1399004714026479. https://www.osti.gov/servlets/purl/1172406.
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@article{osti_1172406,
title = {The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions},
author = {Ruan, Jiapeng and Mouveaux, Thomas and Light, Samuel H. and Minasov, George and Anderson, Wayne F. and Tomavo, Stanislas and Ngô, Huân M.},
abstractNote = {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.},
doi = {10.1107/S1399004714026479},
journal = {Acta Crystallographica. Section D: Biological Crystallography (Online)},
number = 3,
volume = 71,
place = {United States},
year = {Sun Mar 01 00:00:00 EST 2015},
month = {Sun Mar 01 00:00:00 EST 2015}
}
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https://doi.org/10.1107/S1399004714026479
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Works referenced in this record:

Enolase takes part in a macromolecular complex associated to mitochondria in yeast
journal, September 2006

  • Brandina, Irina; Graham, James; Lemaitre-Guillier, Christelle
  • Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1757, Issue 9-10
  • DOI: 10.1016/j.bbabio.2006.07.001

The PILATUS 1M detector
journal, February 2006

  • Broennimann, Ch.; Eikenberry, E. F.; Henrich, B.
  • Journal of Synchrotron Radiation, Vol. 13, Issue 2
  • DOI: 10.1107/S0909049505038665

Expression, Purification and the 1.8Å Resolution Crystal Structure of Human Neuron Specific Enolase
journal, August 2004

  • Chai, Geqing; Brewer, John M.; Lovelace, Leslie L.
  • Journal of Molecular Biology, Vol. 341, Issue 4
  • DOI: 10.1016/j.jmb.2004.05.068

Recognition of Enolase in the Escherichia coli RNA Degradosome
journal, April 2006

Differential expression of two plant-like enolases with distinct enzymatic and antigenic properties during stage conversion of the protozoan parasite Toxoplasma gondii
journal, June 2001

  • Dzierszinski, Florence; Mortuaire, Marlene; Dendouga, Najoua
  • Journal of Molecular Biology, Vol. 309, Issue 5
  • DOI: 10.1006/jmbi.2001.4730

Dynamics of Toxoplasma gondii Differentiation
journal, August 2004

The Protozoan Parasite Toxoplasma gondii Expresses Two Functional Plant-like Glycolytic Enzymes: IMPLICATIONS FOR EVOLUTIONARY ORIGIN OF APICOMPLEXANS
journal, August 1999

  • Dzierszinski, Florence; Popescu, Octavian; Toursel, Catherine
  • Journal of Biological Chemistry, Vol. 274, Issue 35
  • DOI: 10.1074/jbc.274.35.24888

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Evidence for nuclear localisation of two stage-specific isoenzymes of enolase in Toxoplasma gondii correlates with active parasite replication
journal, October 2002

  • Ferguson, David J. P.; Parmley, Stephen F.; Tomavo, Stanislas
  • International Journal for Parasitology, Vol. 32, Issue 11
  • DOI: 10.1016/S0020-7519(02)00129-7

How and why Toxoplasma makes us crazy
journal, April 2013

ToxoDB: an integrated Toxoplasma gondii database resource
journal, December 2007

  • Gajria, B.; Bahl, A.; Brestelli, J.
  • Nucleic Acids Research, Vol. 36, Issue Database
  • DOI: 10.1093/nar/gkm981

Divergent Evolution in Enolase Superfamily: Strategies for Assigning Functions
journal, November 2011

  • Gerlt, John A.; Babbitt, Patricia C.; Jacobson, Matthew P.
  • Journal of Biological Chemistry, Vol. 287, Issue 1
  • DOI: 10.1074/jbc.R111.240945

Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut
journal, September 2011

  • Ghosh, A. K.; Coppens, I.; Gardsvoll, H.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 41
  • DOI: 10.1073/pnas.1103657108

Lateral gene transfer and the complex distribution of insertions in eukaryotic enolase
journal, October 2004

MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2
journal, December 2009

  • Hsu, Kai-Wen; Hsieh, Rong-Hong; Wu, Chew-Wun
  • Molecular Biology of the Cell, Vol. 20, Issue 24
  • DOI: 10.1091/mbc.E09-05-0386

Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective
journal, September 2012

Structure of human α-enolase (hENO1), a multifunctional glycolytic enzyme
journal, May 2008

  • Kang, Hyo Jin; Jung, Suk-Kyeong; Kim, Seung Jun
  • Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 6
  • DOI: 10.1107/S0907444908008561

LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery
journal, October 2011

  • Laskowski, Roman A.; Swindells, Mark B.
  • Journal of Chemical Information and Modeling, Vol. 51, Issue 10
  • DOI: 10.1021/ci200227u

An octamer of enolase from Streptococcus suis
journal, October 2012

Likelihood-enhanced fast translation functions
journal, March 2005

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Storoni, Laurent C.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4
  • DOI: 10.1107/S0907444905001617

Nuclear Glycolytic Enzyme Enolase of Toxoplasma gondii Functions as a Transcriptional Regulator
journal, August 2014

REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011

  • Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444911001314

Structural Features of Protein−Nucleic Acid Recognition Sites †
journal, February 1999

  • Nadassy, Katalin; Wodak, Shoshana J.; Janin, Joël
  • Biochemistry, Vol. 38, Issue 7
  • DOI: 10.1021/bi982362d

Molecular recognition between Escherichia coli enolase and ribonuclease E
journal, August 2010

  • Nurmohamed, Salima; McKay, Adam R.; Robinson, Carol V.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 9
  • DOI: 10.1107/S0907444910030015

Plasmodium falciparum enolase: stage-specific expression and sub-cellular localization
journal, January 2009

  • Pal Bhowmick, Ipsita; Kumar, Nirbhay; Sharma, Shobhona
  • Malaria Journal, Vol. 8, Issue 1
  • DOI: 10.1186/1475-2875-8-179

Sub-cellular localization and post-translational modifications of the Plasmodium yoelii enolase suggest moonlighting functions
journal, January 2007

  • Pal-Bhowmick, Ipsita; Vora, Hardeep K.; Jarori, Gotam K.
  • Malaria Journal, Vol. 6, Issue 1
  • DOI: 10.1186/1475-2875-6-45

Hypoxia induces differential translation of enolase/MBP-1
journal, April 2010

Effect of deletion of a plant like pentapeptide insert on kinetic, structural and immunological properties of enolase from Plasmodium falciparum
journal, May 2009

  • Vora, Hardeep K.; Shaik, Farooque Razvi; Pal-Bhowmick, Ipsita
  • Archives of Biochemistry and Biophysics, Vol. 485, Issue 2
  • DOI: 10.1016/j.abb.2009.02.012

Statistical Analysis of Interface Similarity in Crystals of Homologous Proteins
journal, August 2008

  • Xu, Qifang; Canutescu, Adrian A.; Wang, Guoli
  • Journal of Molecular Biology, Vol. 381, Issue 2
  • DOI: 10.1016/j.jmb.2008.06.002
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    Works referencing / citing this record:

    Syntheses and evaluation of new acridone derivatives for selective binding of oncogene c- myc promoter i-motifs in gene transcriptional regulation
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