title: Structural insights into the interaction of the ribosomal P stalk protein P2 with a type II ribosome-inactivating protein ricin.
abstract: Ricin is a type II ribosome-inactivating protein (RIP) that depurinates A4324at the sarcin-ricin loop of 28 S ribosomal RNA (rRNA), thus inactivating the ribosome by preventing elongation factors from 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 process that RIPs target ribosome. However, the details of the molecular interaction between ricin and P stalk proteins remain unknown. Here, we report the structure of ricin-A chain (RTA) in a complex with the CTD of the human ribosomal protein P2. The structure shows that the Phe111, Leu113and Phe114residues of P2 insert into a hydrophobic pocket formed by the Tyr183, Arg235, Phe240and Ile251residues of RTA, while Asp115of P2 forms hydrogen bonds with Arg235of RTA. The key residues in RTA and P2 for complex formation were mutated, and their importance was determined by pull-down assays. The results from cell-free translation assays further confirmed that the interaction with P stalk proteins is essential for the inhibition of protein synthesis by RTA. Taken together, our results provide a structural basis that will improve our understanding of the process by which ricin targets the ribosome, which will benefit the development of effective small-molecule inhibitors for use as therapeutic agents.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Networks, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.|Key Laboratory of Structural Biology, Hefei Science Center of Chinese Academy of Science, Hefei, Anhui, 230026, People's Republic of China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Fan
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Networks, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.|Key Laboratory of Structural Biology, Hefei Science Center of Chinese Academy of Science, Hefei, Anhui, 230026, People's Republic of China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Networks, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.|Key Laboratory of Structural Biology, Hefei Science Center of Chinese Academy of Science, Hefei, Anhui, 230026, People's Republic of China.
authors.forename: Chongyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Networks, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.|Key Laboratory of Structural Biology, Hefei Science Center of Chinese Academy of Science, Hefei, Anhui, 230026, People's Republic of China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Niu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Networks, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.|Key Laboratory of Structural Biology, Hefei Science Center of Chinese Academy of Science, Hefei, Anhui, 230026, People's Republic of China.
authors.forename: Maikun
authors.initials: M
authors.lastname: Teng
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Networks, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.|Key Laboratory of Structural Biology, Hefei Science Center of Chinese Academy of Science, Hefei, Anhui, 230026, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
mesh_terms: D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*; D012276:Ricin / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal; D012276:Ricin