The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome.
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.
Too
Priscilla Hiu-Mei
PH
Department of Biochemistry, Centre for Protein Science and Crystallography and Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Ma
Meiji Kit-Wan
MK
Mak
Amanda Nga-Sze
AN
Wong
Yuen-Ting
YT
Tung
Christine Kit-Ching
CK
Zhu
Guang
G
Au
Shannon Wing-Ngor
SW
Wong
Kam-Bo
KB
Shaw
Pang-Chui
PC
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*
D010455:Peptides; D010750:Phosphoproteins; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal; C035690:ribosomal phosphoprotein P1; C054675:ribosomal protein P0; D015978:Trichosanthin