Induced DNA bending by unique dimerization of HigA antitoxin

IUCrJ
Jin-Young ParkBong-Jin Lee

Abstract

The bacterial toxin-antitoxin (TA) system regulates cell growth under various environmental stresses. Mycobacterium tuberculosis, the causative pathogen of tuberculosis (TB), has three HigBA type II TA systems with reverse gene organization, consisting of the toxin protein HigB and labile antitoxin protein HigA. Most type II TA modules are transcriptionally autoregulated by the antitoxin itself. In this report, we first present the crystal structure of the M. tuberculosis HigA3 antitoxin (MtHigA3) and MtHigA3 bound to its operator DNA complex. We also investigated the interaction between MtHigA3 and DNA using NMR spectroscopy. The MtHigA3 antitoxin structure is a homodimer that contains a structurally well conserved DNA-binding domain at the N-terminus and a dimerization domain at the C-terminus. Upon comparing the HigA homologue structures, a distinct difference was found in the C-terminal region that possesses the β-lid, and diverse orientations of two helix-turn-helix (HTH) motifs from HigA homologue dimers were observed. The structure of MtHigA3 bound to DNA reveals that the promoter DNA is bound to two HTH motifs of the MtHigA3 dimer presenting 46.5° bending, and the distance between the two HTH motifs of each MtHigA3 mono...Continue Reading

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Methods Mentioned

BETA
environmental stress
NMR
PCR
size-exclusion chromatography
size-exclusion column chromatography
X-ray
PISA
chemical shift
co-crystallization

Software Mentioned

Coot
Autobuild Wizards
PhaserMR
REFMAC5
EMBOSS
APBS
HKL2000
CURVES
ClustalX
PyMol

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