The C-terminal end of P proteins mediates ribosome inactivation by trichosanthin but does not affect the pokeweed antiviral protein activity.
Ribosome inactivating proteins (RIPs) inhibit protein synthesis depurinating a conserved residue in the sarcin/ricin loop of ribosomes. Some RIPs are only active against eukaryotic ribosomes, but other RIPs inactivate with similar efficiency prokaryotic and eukaryotic ribosomes, suggesting that different RIPs would interact with different proteins. The SRL in Trypanosoma cruzi ribosomes is located on a 178b RNA molecule named 28Sdelta. In addition, T. cruzi ribosomes are remarkably resistant to TCS. In spite of these peculiarities, we show that TCS specifically depurinate the predicted A(51) residue on 28Sdelta. We also demonstrated that the C-terminal end of ribosomal P proteins is needed for full activity of the toxin. In contrast to TCS, PAP inactivated efficiently T.cruzi ribosomes, and most importantly, does not require from the C-terminal end of P proteins. These results could explain, at least partially, the different selectivity of these toxins against prokaryotic and eukaryotic ribosomes.
Ayub
Maximiliano Juri
MJ
Fundación Instituto Leloir, IIBBA-CONICET and University of Buenos Aires, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
Smulski
Cristian R
CR
Ma
Kit-Wan
KW
Levin
Mariano J
MJ
Shaw
Pang-Chui
PC
Wong
Kam-Bo
KB
D001665:Binding Sites; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054788:Ribosome Inactivating Proteins / Q000737:chemistry*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry*; D015978:Trichosanthin / Q000737:chemistry*
D004268:DNA-Binding Proteins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D015978:Trichosanthin; D054788:Ribosome Inactivating Proteins; C024275:pokeweed antiviral protein