Database accession: MF2140010
Name: Antitoxin phd dimer (Escherichia virus P1)
PDB ID: 3hs2
Experimental method: X-ray (2.20 Å)
Assembly: Homodimer
Source organism: Escherichia phage P1
Primary publication of the structure:
Garcia-Pino A, Balasubramanian S, Wyns L, Gazit E, De Greve H, Magnuson RD, Charlier D, van Nuland NA, Loris R
Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity.
(2010) Cell 142: 101-11
PMID: 20603017
Abstract:
Regulation of the phd/doc toxin-antitoxin operon involves the toxin Doc as co- or derepressor depending on the ratio between Phd and Doc, a phenomenon known as conditional cooperativity. The mechanism underlying this observed behavior is not understood. Here we show that monomeric Doc engages two Phd dimers on two unrelated binding sites. The binding of Doc to the intrinsically disordered C-terminal domain of Phd structures its N-terminal DNA-binding domain, illustrating allosteric coupling between highly disordered and highly unstable domains. This allosteric effect also couples Doc neutralization to the conditional regulation of transcription. In this way, higher levels of Doc tighten repression up to a point where the accumulation of toxin triggers the production of Phd to counteract its action. Our experiments provide the basis for understanding the mechanism of conditional cooperative regulation of transcription typical of toxin-antitoxin modules. This model may be applicable for the regulation of other biological systems.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA binding DNA binding
DNA-binding transcription repressor activity DNA-binding transcription repressor activity
protein homodimerization activity protein homodimerization activity
sequence-specific DNA binding sequence-specific DNA binding
toxin sequestering activity toxin sequestering activity
Biological process:
negative regulation of DNA-templated transcription negative regulation of DNA-templated transcription
Cellular component:
protein-DNA complex protein-DNA complex
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: According to the most probable oligomerization state stored in PDBe G chains were not considered.
Number of unique protein segments: 1
Name: Antitoxin phd
Source organism: Escherichia phage P1
Length: 73 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMQSINFRTARGNLSEVLNNVEAGEEVEITRRGREPAVIVSKATFEAYKKAALDAEFASLFDTLDSTNKELVNR
UniProtKB AC: Q06253 (positions: 1-56)
Coverage: 76%
Name: Antitoxin phd
Source organism: Escherichia phage P1
Length: 73 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMQSINFRTARGNLSEVLNNVEAGEEVEITRRGREPAVIVSKATFEAYKKAALDAEFASLFDTLDSTNKELVNR
UniProtKB AC: Q06253 (positions: 1-56)
Coverage: 76%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Antitoxin Phd_YefM
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The dimerization of the prevents host death (phd) antitoxin from Escherichia virus P1 has been shown with differential scanning calorimetry to fit well to a two-state model consisting of a dimer unfolding into monomer species (PMID:20603017).
Chain A:
The region(s) described in DP00288 covers 100% of the sequence present in the structure
Chain B:
The region(s) described in DP00288 covers 100% of the sequence present in the structure
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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