title: The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome.
abstract: Ribosome-inactivating proteins (RIPs) inhibit protein synthesis by enzymatically depurinating a specific adenine residue at the sarcin-ricin loop of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation centre of the ribosome. Here, we present the 2.2 A crystal structure of trichosanthin (TCS) complexed to the peptide SDDDMGFGLFD, which corresponds to the conserved C-terminal elongation factor binding domain of the ribosomal P protein. The N-terminal region of this peptide interacts with Lys173, Arg174 and Lys177 in TCS, while the C-terminal region is inserted into a hydrophobic pocket. The interaction with the P protein contributes to the ribosome-inactivating activity of TCS. This 11-mer C-terminal P peptide can be docked with selected important plant and bacterial RIPs, indicating that a similar interaction may also occur with other RIPs.
authors.affiliation: Department of Biochemistry, Centre for Protein Science and Crystallography and Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors.forename: Priscilla Hiu-Mei
authors.initials: PH
authors.lastname: Too
authors.forename: Meiji Kit-Wan
authors.initials: MK
authors.lastname: Ma
authors.forename: Amanda Nga-Sze
authors.initials: AN
authors.lastname: Mak
authors.forename: Yuen-Ting
authors.initials: YT
authors.lastname: Wong
authors.forename: Christine Kit-Ching
authors.initials: CK
authors.lastname: Tung
authors.forename: Guang
authors.initials: G
authors.lastname: Zhu
authors.forename: Shannon Wing-Ngor
authors.initials: SW
authors.lastname: Au
authors.forename: Kam-Bo
authors.initials: KB
authors.lastname: Wong
authors.forename: Pang-Chui
authors.initials: PC
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D015978:Trichosanthin / Q000737:chemistry*
chemical_list: D010455:Peptides; D010750:Phosphoproteins; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal; C035690:ribosomal phosphoprotein P1; C054675:ribosomal protein P0; D015978:Trichosanthin