9BBF

Structure of Clostridioides difficile Component A (50-463) in Complex with a CDTb Oligomer

9BBF の概要

• エントリーDOI: 10.2210/pdb9bbf/pdb
• EMDBエントリー: 44419
• 分子名称: ADP-ribosyltransferase binding component, ADP-ribosyltransferase enzymatic component, CALCIUM ION (3 entities in total)
• 機能のキーワード: clostridioides, difficile, toxin, cdt, transferase
• 由来する生物種: Clostridioides difficile; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 708213.27

構造登録者

Sheedlo, M.J.,Mullard, R.M. (登録日: 2024-04-05, 公開日: 2024-11-27, 最終更新日: 2026-06-10)

主引用文献

Mullard, R.M.,Sheedlo, M.J.
The N-terminus of the Clostridioides difficile transferase A component directs toxin activity and potency.
Mbio, 16:e0240524-e0240524, 2025

PubMed Abstract: infection is the leading cause of antibiotic-associated, hospital-acquired diarrhea in the USA; the pathology of which is mediated by toxins. The presence of a toxin known as the Transferase (CDT) in some clinical isolates is linked to severe symptoms including increased incidence of reinfection and higher rates of mortality. Despite its apparent importance to pathology, a mechanistic model of how CDT intoxicates cells remains incomplete. Here, we describe a motif composed of acidic and basic residues (the KDKEK motif) that is essential for toxin function. Using Cryogenic Electron Microscopy (Cryo-EM), we highlight an orientation of the KDKEK motif wherein the acidic residues engage structures thought to play an important role during toxin delivery. We thus present a model wherein these interactions prime CDT for entry into host cells. We expect that this model can be extrapolated to other bacterial toxins to understand how they enter cells.IMPORTANCE is the leading cause of hospital-acquired infectious diarrhea in the USA. The pathology that accompanies infection is triggered by toxins produced by the bacterium. One of these, the Transferase (CDT), has been associated with poorer patient outcomes, although a direct connection to CDT activity has remained elusive. Herein, we present new insight into the mechanism of CDT intoxication and define two regions of the toxin as important for its activity. Moreover, we have generated mutants of CDT that retain the ability to assemble but can no longer intoxicate host cells. In the future, we expect these mutants will serve as valuable tools to help elucidate the role of CDT during infection.

PubMed: 39611841
DOI: 10.1128/mbio.02405-24

実験手法

ELECTRON MICROSCOPY (3.6 Å)