title: Crystal Structure of Ribosome-Inactivating Protein Ricin A Chain in Complex with the C-Terminal Peptide of the Ribosomal Stalk Protein P2.
abstract: Ricin is a type 2 ribosome-inactivating protein (RIP), containing a catalytic A chain and a lectin-like B chain. It inhibits protein synthesis by depurinating the N-glycosidic bond at α-sarcin/ricin loop (SRL) of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation center of the ribosome. Here, we present the 1.6 Å crystal structure of Ricin A chain (RTA) complexed to the C-terminal peptide of the ribosomal stalk protein P2, which plays a crucial role in specific recognition of elongation factors and recruitment of eukaryote-specific RIPs to the ribosomes. Our structure reveals that the C-terminal GFGLFD motif of P2 peptide is inserted into a hydrophobic pocket of RTA, while the interaction assays demonstrate the structurally untraced SDDDM motif of P2 peptide contributes to the interaction with RTA. This interaction mode of RTA and P protein is in contrast to that with trichosanthin (TCS), Shiga-toxin (Stx) and the active form of maize RIP (MOD), implying the flexibility of the P2 peptide-RIP interaction, for the latter to gain access to ribosome.
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Shiww@cuhk.edu.hk.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shi
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. samtys0910@gmail.com.
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Tang
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. seeyuen123@gmail.com.
authors.forename: See-Yuen
authors.initials: SY
authors.lastname: Sze
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. janet.chuk@gmail.com.
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Zhu
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. kbwong@cuhk.edu.hk.
authors.forename: Kam-Bo
authors.initials: KB
authors.lastname: Wong
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. pcshaw@cuhk.edu.hk.
authors.forename: Pang-Chui
authors.initials: PC
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry*; D011487:Protein Conformation; D012269:Ribosomal Proteins / Q000737:chemistry*; D012276:Ricin / Q000737:chemistry* / Q000235:genetics; D022621:Shiga Toxin / Q000737:chemistry; D015978:Trichosanthin / Q000737:chemistry
chemical_list: D010455:Peptides; D010750:Phosphoproteins; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal; D015978:Trichosanthin; D022621:Shiga Toxin; D012276:Ricin
keywords: Ricin; ribosomal P stalk protein; ribosome; ribosome-inactivating protein