General Information

Database accession: MF2120024 Original MFIB entry

Name: Antitoxin phd dimer (Mycobacterium tuberculosis)

PDB ID: 3g5o PDBe

Experimental method: X-ray (2.00 Å)

Assembly: Homodimer

Source organism: Mycobacterium tuberculosis

Primer publication of the structure:

Miallau L, Jain P, Arbing MA, Cascio D, Phan T, Ahn CJ, Chan S, Chernishof I, Maxson M, Chiang J, Jacobs WR, Eisenberg DS
Comparative proteomics identifies the cell-associated lethality of M. tuberculosis RelBE-like toxin-antitoxin complexes.

(2013) Structure 21: 627-37

PMID: 23523424 PubMed

Abstract:

The Mycobacterium tuberculosis (Mtb) genome encodes approximately 90 toxin-antitoxin protein complexes, including three RelBE family members, which are believed to play a major role in bacterial fitness and pathogenicity. We have determined the crystal structures of Mtb RelBE-2 and RelBE-3, and the structures reveal homologous heterotetramers. Our structures suggest RelE-2, and by extension the closely related RelE-1, use a different catalytic mechanism than RelE-3, because our analysis of the RelE-2 structure predicts additional amino acid residues that are likely to be functionally significant and are missing from analogous positions in the RelE-3 structure. Toxicity assays corroborate our structural findings; overexpression of RelE-3, whose active site is more similar to Escherichia coli YoeB, has limited consequences on bacterial growth, whereas RelE-1 and RelE-2 overexpression results in acute toxicity. Moreover, RelE-2 overexpression results in an elongated cell phenotype in Mycobacterium smegmatis and protects M. tuberculosis against antibiotics, suggesting a different functional role for RelE-2.


Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

DNA binding DNA binding GeneOntology

toxin-antitoxin pair type II binding toxin sequestering activity GeneOntology

Biological process:

regulation of transcription, DNA-templated regulation of DNA-templated transcription GeneOntology

positive regulation of growth positive regulation of growth GeneOntology

transcription, DNA-templated DNA-templated transcription GeneOntology

Cellular component: not assigned

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: A, D

Notes: Chains B and C were removed as chains A and D represent the biologically relevant dimer. Chains A and D were truncated to exclude the regions in contact with chains B and C.

Number of unique protein segments: 1


Chain A

Name: Antitoxin RelF

Source organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Length: 93 residues

Sequence:Sequence according to the corresponding UniProt protein segmentMRILPISTIKGKLNEFVDAVSSTQDQITITKNGAPAAVLVGADEWESLQETLYWLAQPGIRESIAEADADIASGRTYGEDEIRAEFGVPRRPH

UniProtKB AC: O33347 (positions: 1-93) UniProt

UniRef90 AC: UniRef90_O33347 (positions: 1-93) UniRef90

Chain D

Name: Antitoxin RelF

Source organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Length: 93 residues

Sequence:Sequence according to the corresponding UniProt protein segmentMRILPISTIKGKLNEFVDAVSSTQDQITITKNGAPAAVLVGADEWESLQETLYWLAQPGIRESIAEADADIASGRTYGEDEIRAEFGVPRRPH

UniProtKB AC: O33347 (positions: 1-93) UniProt

UniRef90 AC: UniRef90_O33347 (positions: 1-93) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Evidence level: Direct evidence

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:

A homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.

Chain D:

A homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.

The molecule viewer shows our modified stucture.

Download the CIF file (.gz.cif)

Download this entry's XML file (.xml)