Crystal Structure of Ribosome-Inactivating Protein Ricin A Chain in Complex with the C-Terminal Peptide of the Ribosomal Stalk Protein P2

Toxins (Basel). 2016 Oct 13;8(10):296. doi: 10.3390/toxins8100296.


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.

Keywords: Ricin; ribosomal P stalk protein; ribosome; ribosome-inactivating protein.

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Peptides / chemistry
  • Phosphoproteins / chemistry*
  • Protein Conformation
  • Ribosomal Proteins / chemistry*
  • Ricin / chemistry*
  • Ricin / genetics
  • Shiga Toxin / chemistry
  • Trichosanthin / chemistry


  • Peptides
  • Phosphoproteins
  • Ribosomal Proteins
  • phosphoprotein P2, ribosomal
  • Trichosanthin
  • Shiga Toxin
  • Ricin