Trichosanthin interacts with acidic ribosomal proteins P0 and P1 and mitotic checkpoint protein MAD2B

Trichosanthin is a ribosome-inactivating protein with multiple pharmacologi cal properties. By a yeast two-hybrid system, ribosomal phosphoproteins P0 and P1 and a putative mitotic checkpoint protein, MAD2B, were found to inte ract with an active-site mutated trichosanthin (TCS). The interactions were verified by an in vitro binding assay of recombinant wild-type TCS and tar get proteins. The interaction domain of PO was mapped to amino acids 220-27 3, which had been previously reported to be involved in the interaction wit h P1 and P2 in yeast. Consistent with our previous finding that the last se ven residues of TCS are not essential for an active conformation, the same deletion did not affect the interaction with P0. Our present study suggests that TCS may disrupt the binding of elongation factors to the P-complex, i n addition to the well-known N-glycosidase activity for ribosome inactivati on.