RESUMEN
Prokaryotic pathogens have developed specialized mechanisms for efficient uptake of ferrous iron (Fe(2+)) from the host. In Legionella pneumophila, the causative agent of Legionnaires' disease, the transmembrane GTPase FeoB plays a key role in Fe(2+) acquisition and virulence. FeoB consists of a membrane-embedded core and an N-terminal, cytosolic region (NFeoB). Here, we report the crystal structure of NFeoB from L. pneumophila, revealing a monomeric protein comprising two separate domains with GTPase and guanine-nucleotide dissociation inhibitor (GDI) functions. The GDI domain displays a novel fold, whereas the overall structure of the GTPase domain resembles that of known G domains but is in the rarely observed nucleotide-free state.
Asunto(s)
Hierro/metabolismo , Legionella pneumophila/química , Proteínas de Transporte de Membrana/química , Estructura Terciaria de Proteína , Secuencia de Aminoácidos , Sitios de Unión/genética , Dominio Catalítico , GTP Fosfohidrolasas/metabolismo , Inhibidores de Disociación de Guanina Nucleótido/metabolismo , Legionella pneumophila/genética , Legionella pneumophila/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Pliegue de Proteína , Estructura Cuaternaria de Proteína , Estructura Secundaria de Proteína , Difracción de Rayos XRESUMEN
The facultative intracellular pathogen Salmonella enterica causes a variety of diseases, including gastroenteritis and typhoid fever. Inside epithelial cells, Salmonella replicates in vacuoles, which localize in the perinuclear area in close proximity to the Golgi apparatus. Among the effector proteins translocated by the Salmonella pathogenicity island 2-encoded type III secretion system, SifA and SseG have been shown necessary but not sufficient to ensure the intracellular positioning of Salmonella vacuoles. Hence, we have investigated the involvement of other secreted effector proteins in this process. Here we show that SseF interacts functionally and physically with SseG but not SifA and is also required for the perinuclear localization of Salmonella vacuoles. The observations show that the intracellular positioning of Salmonella vacuoles is a complex phenomenon resulting from the combined action of several effector proteins.
