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| Title | Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk reveals residues involved in the binding interaction. |
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| Journal, issue, pages | J Biol Chem, Vol. 299, Issue 1, Page 102795, Year 2023 |
| Publish date | Dec 15, 2022 |
 Authors | Arkadiusz W Kulczyk / Carlos Oscar S Sorzano / Przemysław Grela / Marek Tchórzewski / Nilgun E Tumer / Xiao-Ping Li /    |
| PubMed Abstract | Shiga toxin 2a (Stx2a) is the virulence factor of enterohemorrhagic Escherichia coli. The catalytic A1 subunit of Stx2a (Stx2A1) interacts with the ribosomal P-stalk for loading onto the ribosome and ...Shiga toxin 2a (Stx2a) is the virulence factor of enterohemorrhagic Escherichia coli. The catalytic A1 subunit of Stx2a (Stx2A1) interacts with the ribosomal P-stalk for loading onto the ribosome and depurination of the sarcin-ricin loop, which halts protein synthesis. Because of the intrinsic flexibility of the P-stalk, a structure of the Stx2a-P-stalk complex is currently unknown. We demonstrated that the native P-stalk pentamer binds to Stx2a with nanomolar affinity, and we employed cryo-EM to determine a structure of the 72 kDa Stx2a complexed with the P-stalk. The structure identifies Stx2A1 residues involved in binding and reveals that Stx2a is anchored to the P-stalk via only the last six amino acids from the C-terminal domain of a single P-protein. For the first time, the cryo-EM structure shows the loop connecting Stx2A1 and Stx2A2, which is critical for activation of the toxin. Our principal component analysis of the cryo-EM data reveals the intrinsic dynamics of the Stx2a-P-stalk interaction, including conformational changes in the P-stalk binding site occurring upon complex formation. Our computational analysis unveils the propensity for structural rearrangements within the C-terminal domain, with its C-terminal six amino acids transitioning from a random coil to an α-helix upon binding to Stx2a. In conclusion, our cryo-EM structure sheds new light into the dynamics of the Stx2a-P-stalk interaction and indicates that the binding interface between Stx2a and the P-stalk is the potential target for drug discovery. |
 External links | J Biol Chem / PubMed:36528064 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.1 - 4.5 Å |
| Structure data |  EMDB-26380: Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk EMDB-26381, PDB-7u6v: |
| Chemicals |  ChemComp-HOH: |
| Source |
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 Keywords |  TOXIN / Shiga toxin 2 / Ribosomal P-stalk / Complex |
