7Z7H

Structure of P. luminescens TccC3-F-actin complex

Summary for 7Z7H

• Entry DOI: 10.2210/pdb7z7h/pdb
• EMDB information: 14532
• Descriptor: Actin, alpha skeletal muscle, Maltose/maltodextrin-binding periplasmic protein,TccC3, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: bacterial toxin, f-actin, toxin
• Biological source: Photorhabdus luminescens; More
• Total number of polymer chains: 6
• Total formula weight: 277147.79

Authors

Belyy, A.,Raunser, S. (deposition date: 2022-03-15, release date: 2022-06-29, Last modification date: 2023-03-15)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.8 Å)