The intrinsically disordered domain of the antitoxin Phd chaperones the toxin Doc against irreversible inactivation and misfolding.

TitleThe intrinsically disordered domain of the antitoxin Phd chaperones the toxin Doc against irreversible inactivation and misfolding.
Publication TypeJournal Article
Year of Publication2014
AuthorsDe Gieter, S., A. Konijnenberg, A. Talavera, A. Butterer, S. Haesaerts, H. De Greve, F. Sobott, R. Loris, and A. Garcia-Pino
JournalJ Biol Chem
Volume289
Issue49
Pagination34013-23
Date Published2014 Dec 05
ISSN1083-351X
KeywordsBacteriophage P1, Crystallography, X-Ray, Escherichia coli, Gene Expression Regulation, Viral, Models, Molecular, Molecular Chaperones, Protein Folding, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Thermodynamics, Viral Proteins
Abstract

The toxin Doc from the phd/doc toxin-antitoxin module targets the cellular translation machinery and is inhibited by its antitoxin partner Phd. Here we show that Phd also functions as a chaperone, keeping Doc in an active, correctly folded conformation. In the absence of Phd, Doc exists in a relatively expanded state that is prone to dimerization through domain swapping with its active site loop acting as hinge region. The domain-swapped dimer is not capable of arresting protein synthesis in vitro, whereas the Doc monomer is. Upon binding to Phd, Doc becomes more compact and is secured in its monomeric state with a neutralized active site.

DOI10.1074/jbc.M114.572396
Alternate JournalJ. Biol. Chem.
PubMed ID25326388
PubMed Central IDPMC4256337
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