ROP2 from Toxoplasma gondii: A Virulence Factor with a Protein-Kinase Fold and No Enzymatic Activity

Gilles Labesse; Muriel Gelin; Yannick Bessin; Maryse Lebrun; Julien Papoin; Rachel Cerdan; Stefan T. Arold; Jean François Dubremetz

doi:10.1016/j.str.2008.11.005

ROP2 from Toxoplasma gondii: A Virulence Factor with a Protein-Kinase Fold and No Enzymatic Activity

Gilles Labesse^*, Muriel Gelin, Yannick Bessin, Maryse Lebrun, Julien Papoin, Rachel Cerdan, Stefan T. Arold, Jean François Dubremetz

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

The ROP2 protein and its paralogs are important virulence factors secreted into the host cell by the parasite Toxoplasma gondii. Here we describe the crystal structure of a large and soluble domain of mature ROP2, representative of the ROP2-like protein family. This is a structure of a protein-kinase fold that is devoid of catalytic residues and does not bind ATP. Various structural extensions constitute a signature of this protein family and act to maintain the protein kinase in an open conformation. Our ROP2 structure rules out a previous structural model of attachment of ROP2-like proteins to the parasitophorous vacuole membrane. We propose an alternative mode of membrane attachment implicating basic and amphiphatic helices present in the flexible N terminus of ROP2.

Original language	English (US)
Pages (from-to)	139-146
Number of pages	8
Journal	Structure
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.str.2008.11.005
State	Published - Jan 14 2009
Externally published	Yes

Bibliographical note

Funding Information:
We acknowledge help from Hélène Déméné, Karine De Guillen, and Martin Cohen-Gonsaud for the recording of NMR and UV-CD spectra. We thank D. Svergun and his colleagues for assistance with SAXS data recording and analysis at the X33 beamline at EMBL/DESY, Hamburg. The authors thank Sergio Angel for providing the pQE-Rop2B plasmid. We acknowledge support from European Community—Research Infrastructure Action under the FP6 (RII3/CT/2004/5060008) for access to EMBL/DESY, Hamburg. We thank the ESRF staff for their help in recording diffraction data on beamlines ID14 and ID29. This work was supported by ANR-06-MIME-024-01.

Keywords

MICROBIO

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1016/j.str.2008.11.005

Cite this

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title = "ROP2 from Toxoplasma gondii: A Virulence Factor with a Protein-Kinase Fold and No Enzymatic Activity",

abstract = "The ROP2 protein and its paralogs are important virulence factors secreted into the host cell by the parasite Toxoplasma gondii. Here we describe the crystal structure of a large and soluble domain of mature ROP2, representative of the ROP2-like protein family. This is a structure of a protein-kinase fold that is devoid of catalytic residues and does not bind ATP. Various structural extensions constitute a signature of this protein family and act to maintain the protein kinase in an open conformation. Our ROP2 structure rules out a previous structural model of attachment of ROP2-like proteins to the parasitophorous vacuole membrane. We propose an alternative mode of membrane attachment implicating basic and amphiphatic helices present in the flexible N terminus of ROP2.",

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note = "Funding Information: We acknowledge help from H{\'e}l{\`e}ne D{\'e}m{\'e}n{\'e}, Karine De Guillen, and Martin Cohen-Gonsaud for the recording of NMR and UV-CD spectra. We thank D. Svergun and his colleagues for assistance with SAXS data recording and analysis at the X33 beamline at EMBL/DESY, Hamburg. The authors thank Sergio Angel for providing the pQE-Rop2B plasmid. We acknowledge support from European Community—Research Infrastructure Action under the FP6 (RII3/CT/2004/5060008) for access to EMBL/DESY, Hamburg. We thank the ESRF staff for their help in recording diffraction data on beamlines ID14 and ID29. This work was supported by ANR-06-MIME-024-01. ",

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AU - Lebrun, Maryse

AU - Papoin, Julien

AU - Cerdan, Rachel

AU - Arold, Stefan T.

AU - Dubremetz, Jean François

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ROP2 from Toxoplasma gondii: A Virulence Factor with a Protein-Kinase Fold and No Enzymatic Activity

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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