7ZBQ

Structure of the ADP-ribosyltransferase TccC3HVR from Photorhabdus Luminescens

7ZBQ の概要

• エントリーDOI: 10.2210/pdb7zbq/pdb
• NMR情報: BMRB: 34717
• 分子名称: TccC3 (1 entity in total)
• 機能のキーワード: adp-ribosylation, r-s-e motif, actin modification, toxin
• 由来する生物種: Photorhabdus luminescens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21723.78

構造登録者

Lindemann, F.,Belyy, A.,Friedrich, D.,Schmieder, P.,Bardiaux, B.,Roderer, D.,Funk, J.,Protze, J.,Bieling, P.,Oschkinat, H.,Raunser, S. (登録日: 2022-03-24, 公開日: 2022-06-29, 最終更新日: 2024-06-19)

主引用文献

Belyy, A.,Lindemann, F.,Roderer, D.,Funk, J.,Bardiaux, B.,Protze, J.,Bieling, P.,Oschkinat, H.,Raunser, S.
Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin.
Nat Commun, 13:4202-4202, 2022

PubMed Abstract: Tc toxins deliver toxic enzymes into host cells by a unique injection mechanism. One of these enzymes is the actin ADP-ribosyltransferase TccC3, whose activity leads to the clustering of the cellular cytoskeleton and ultimately cell death. Here, we show in atomic detail how TccC3 modifies actin. We find that the ADP-ribosyltransferase does not bind to G-actin but interacts with two consecutive actin subunits of F-actin. The binding of TccC3 to F-actin occurs via an induced-fit mechanism that facilitates access of NAD to the nucleotide binding pocket. The following nucleophilic substitution reaction results in the transfer of ADP-ribose to threonine-148 of F-actin. We demonstrate that this site-specific modification of F-actin prevents its interaction with depolymerization factors, such as cofilin, which impairs actin network turnover and leads to steady actin polymerization. Our findings reveal in atomic detail a mechanism of action of a bacterial toxin through specific targeting and modification of F-actin.

PubMed: 35858890
DOI: 10.1038/s41467-022-31836-w

実験手法

SOLUTION NMR