title: The intrinsically disordered domain of the antitoxin Phd chaperones the toxin Doc against irreversible inactivation and misfolding.
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.
authors.affiliation: From Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, Molecular Recognition Unit (MoRe).
authors.forename: Steven
authors.initials: S
authors.lastname: De Gieter
authors.affiliation: Biomolecular and Analytical Mass Spectrometry group, Department of Chemistry and.
authors.forename: Albert
authors.initials: A
authors.lastname: Konijnenberg
authors.affiliation: From Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, Molecular Recognition Unit (MoRe).
authors.forename: Ariel
authors.initials: A
authors.lastname: Talavera
authors.affiliation: Biomolecular and Analytical Mass Spectrometry group, Department of Chemistry and.
authors.forename: Annika
authors.initials: A
authors.lastname: Butterer
authors.affiliation: From Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, Molecular Recognition Unit (MoRe).
authors.forename: Sarah
authors.initials: S
authors.lastname: Haesaerts
authors.affiliation: From Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), Pleinlaan 2, B-1050 Brussels, Belgium, and.
authors.forename: Henri
authors.initials: H
authors.lastname: De Greve
authors.affiliation: Biomolecular and Analytical Mass Spectrometry group, Department of Chemistry and Center for Proteomics (CFP-CeProMa), University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerpen, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.affiliation: From Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, Molecular Recognition Unit (MoRe).
authors.forename: Remy
authors.initials: R
authors.lastname: Loris
authors.affiliation: From Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, Molecular Recognition Unit (MoRe), agarciap@vub.ac.be.
authors.forename: Abel
authors.initials: A
authors.lastname: Garcia-Pino
mesh_terms: D017101:Bacteriophage P1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C083664:Doc protein, Enterobacteria phage P1; D018832:Molecular Chaperones; C083665:Phd protein, Enterobacteria phage P1; D014764:Viral Proteins
keywords: Chaperone; Chemical Biology; Crystal Structure; Doc; Fic; Phd; Phosphorylation Enzyme; Small Angle X-ray Scattering; Toxin-Antitoxin; Translation Control