8QEO

cryo-EM structure complex of Frizzled-7 and Clostridioides difficile toxin B

8QEO の概要

• エントリーDOI: 10.2210/pdb8qeo/pdb
• EMDBエントリー: 18373 18374
• 分子名称: Toxin B, Frizzled-7, ZINC ION (3 entities in total)
• 機能のキーワード: micriobiology, class f g protein-coupled receptors, crop dynamics, toxin
• 由来する生物種: Clostridioides difficile; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 341077.83

構造登録者

Kinsolving, J.,Bous, J. (登録日: 2023-09-01, 公開日: 2024-03-20, 最終更新日: 2024-11-06)

主引用文献

Kinsolving, J.,Bous, J.,Kozielewicz, P.,Kosenina, S.,Shekhani, R.,Gratz, L.,Masuyer, G.,Wang, Y.,Stenmark, P.,Dong, M.,Schulte, G.
Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD 7.
Cell Rep, 43:113727-113727, 2024

PubMed Abstract: The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD, are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible for pathogenesis associated with Clostridioides difficile infection. We employ a live-cell assay examining the affinity between full-length FZDs and TcdB. Moreover, we present cryoelectron microscopy structures of TcdB alone and in complex with full-length FZD, which reveal that large structural rearrangements of the combined repetitive polypeptide domain are required for interaction with FZDs and other TcdB receptors, constituting a first step for receptor recognition. Furthermore, we show that bezlotoxumab, an FDA-approved monoclonal antibody to treat Clostridioides difficile infection, favors the apo-TcdB structure and thus disrupts binding with FZD. The dynamic transition between the two conformations of TcdB also governs the stability of the pore-forming region. Thus, our work provides structural and functional insight into how conformational dynamics of TcdB determine receptor binding.

PubMed: 38308843
DOI: 10.1016/j.celrep.2024.113727

実験手法

ELECTRON MICROSCOPY (3.26 Å)