7U6V

Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk

7U6V の概要

• エントリーDOI: 10.2210/pdb7u6v/pdb
• EMDBエントリー: 26380 26381
• 分子名称: Shiga toxin 2a subunit A (Stx2A), Shiga toxin 2a subunit B (Stx2B), C-terminal domain (CTD) from the Ribosomal P-stalk, ... (4 entities in total)
• 機能のキーワード: shiga toxin 2, ribosomal p-stalk, complex, toxin
• 由来する生物種: Shigella dysenteriae; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 72991.85

構造登録者

Kulczyk, A.W. (登録日: 2022-03-06, 公開日: 2023-01-11, 最終更新日: 2024-11-13)

主引用文献

Kulczyk, A.W.,Sorzano, C.O.S.,Grela, P.,Tchorzewski, M.,Tumer, N.E.,Li, X.P.
Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk reveals residues involved in the binding interaction.
J.Biol.Chem., 299:102795-102795, 2022

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 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.

PubMed: 36528064
DOI: 10.1016/j.jbc.2022.102795

実験手法

ELECTRON MICROSCOPY (4.1 Å)