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.
authors.affiliation: Atelier de Bio- et Chimie Informatique Structurale, Centre de Biochimie Structurale, CNRS, UMR5048, Universités Montpellier 1 et 2, F34090 Montpellier, France. labesse@cbs.cnrs.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Labesse
authors.forename: Muriel
authors.initials: M
authors.lastname: Gelin
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bessin
authors.forename: Maryse
authors.initials: M
authors.lastname: Lebrun
authors.forename: Julien
authors.initials: J
authors.lastname: Papoin
authors.forename: Rachel
authors.initials: R
authors.lastname: Cerdan
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002942:Circular Dichroism; D006224:Cricetinae; D017931:DNA Primers; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000378:metabolism; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014122:Toxoplasma / Q000737:chemistry* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D010455:Peptides; D015800:Protozoan Proteins; C090555:ROP 2 protein, Toxoplasma gondii; D011494:Protein Kinases