Ricin is a type Ⅱ ribosome-inactivating protein(RIP).It depurinates the A4324 at the sarcin-ricin loop of 28S rRNA,which thereby inactivates ribosome by preventing elongation factors binding to the GTPase activation centre.Recent studies have disclosed that the conserved C-terminal domain(CTD)of eukaryotic ribosomal P stalk proteins is involved in the targeting of RIPs to the ribosome,however the detailed molecular interaction model of Ricin with P stalk proteins remains unknown.Here,we report the complex structure of Ricin-A chain(RTA)with the CTD of human ribosomal protein P2.The structure shows that residues Leu113 and Phe114 of P2 insert into a hydrophobic pocket formed by residues Tyr183,Arg235,Phe240 and Ile251 of RTA,while residue Asp115 of P2 makes hydrogen bonds to Arg235 of RTA.The key residues on RTA and P2 for the complex formation were mutated and their importance was determined by pull-down assay.Cell-free translation results further confirm that the interaction with P stalk proteins is essential for the ribosome-inactivating activity of RTA.Taken together,our results provide a structural basis for better understanding the process of ribosome targeting of Ricin,which is of benefit to the development of effective small-molecule inhibitors as therapeutics.