Thioredoxin 1 moonlights as a chaperone for an interbacterial ADP-ribosyltransferase toxin

Abstract Formation and breakage of disulfide bridges strongly impacts folding and activity of proteins. Thioredoxin 1 (TrxA) is a small, conserved enzyme that reduces disulfide bonds in the bacterial cytosol. In this study, we provide an example of the emergence of a chaperone role for TrxA, which i...

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Bibliographic Details
Main Authors: Baptiste Dumont, Laurent Terradot, Eric Cascales, Laurence Van Melderen, Dukas Jurėnas
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54892-w
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Summary:Abstract Formation and breakage of disulfide bridges strongly impacts folding and activity of proteins. Thioredoxin 1 (TrxA) is a small, conserved enzyme that reduces disulfide bonds in the bacterial cytosol. In this study, we provide an example of the emergence of a chaperone role for TrxA, which is independent of redox catalysis. We show that the activity of the secreted bacterial ADP-ribosyltransferase (ART) toxin TreX, which does not contain any cysteines, is dependent on TrxA. TreX binds to the reduced form of TrxA via its carboxy-terminal extension to form a soluble and active complex. Structural studies revealed that TreX-like toxins are homologous to Scabin-like ART toxins which possess cysteine residues and form disulfide bridges at the position that superimposes the TrxA binding site in TreX. Our study therefore suggests that thioredoxin 1 evolved alternative functions by maintaining the interaction with cysteine-free substrates.
ISSN:2041-1723