C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome

• Published in: Nucleic acids research Vol. 37; no. 2; pp. 602 - 610
• Main Authors: Too, Priscilla Hiu-Mei, Ma, Meiji Kit-Wan, Mak, Amanda Nga-Sze, Wong, Yuen-Ting, Tung, Christine Kit-Ching, Zhu, Guang, Au, Shannon Wing-Ngor, Wong, Kam-Bo, Shaw, Pang-Chui
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2009; Oxford Publishing Limited (England)
• Subjects: Amino Acid Sequence; Models, Molecular; Molecular Sequence Data; Peptides - chemistry; Phosphoproteins - chemistry; Protein Structure, Tertiary; Ribosomal Proteins - chemistry; Sequence Homology, Amino Acid; Structural Biology; Trichosanthin - chemistry
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkn922

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 Å 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.