INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Protein toxins as tools for studying unique features of the Trypanosoma cruzi ribosomes
Autor/es:
JURI AYUB M, SMULSKI CR, GÓMEZ K, LEVIN MJ, ALGRANATI ID
Lugar:
Rosario, Santa Fe, Argentina
Reunión:
Congreso; VIII Congreso Argentina de Protozoología y Enfermedades Parasitarias (SAP); 2008
Institución organizadora:
Sociedad Argentina de Protozoología
Resumen:
With the aim of identifying unique functional features in trypanosomatid ribosomes, we have evaluated the effect of different Ribosome Inactivating Proteins (RIPs). These toxins selectively depurinate an adenine residue on the highly conserved Sarcin Ricin Loop (SRL) of the 28S rRNA. Recently we demonstrated that T. cruzi ribosomes are >1,000 times more resistant to Trichosanthin (TCS) than mammalian particles. On the contrary, Pokeweed Antiviral Protein (PAP) is equally effective against both types of ribosomes. We also demonstrated that these toxins interact with different ribosomal proteins. In the present work, we tested two recently described RIPs; Pulchellin and ME1. The sequence analysis of these proteins suggested some putative amino acids involved in activity against T. cruzi ribosomes. Finally, in order to dissect the molecular mechanism of resistance to TCS, its affinity against mammalian and T. cruzi ribosomes was measured. Interestingly, the affinity by parasite ribosomes was 10 times lower. This could only partially account for the >1,000 fold decreased activity, strongly suggesting variations in the catalytic efficiency (kcat) as the main mechanism. Altogether, our analysis show that the SRL neighbouring region shows important differences between mammalian and trypanosomatids, and could be an adequate target for development of anti-parasitic drugs.