SNAP annotations: PDB entry 9chl

PDB-id

9chl; DSSR-derived features in text and JSON formats; DNAproDB

Class

antitoxin-DNA binding protein-DNA

Method

X-ray (2.4 Å)

Summary

P. vulgaris tetrameric higba- operator 2 DNA

Reference

Pavelich IJ, Schureck MA, Srinivas P, Blackburn TM, Wang D, Hoffer ED, Boamah M, Zaldana K, Onuoha N, Miles SJ, Grabowicz M, Okafor CD, Dunham CM (2025): "Antitoxin control of optimal transcriptional repression in the atypical HigB-HigA toxin-antitoxin system from Proteus vulgaris." Nucleic Acids Res., 53. doi: 10.1093/nar/gkaf610.

Abstract

Bacterial toxin-antitoxin (TA) pairs transcriptionally autoregulate their expression via a repression/derepression mechanism in response to changing environmental conditions. The structural diversity of TA systems influences the mechanisms of transcriptional regulation. Here, we define the molecular mechanism for the plasmid-encoded HigB-HigA TA pair originally identified in a post-operative infection with antibiotic-resistant Proteus vulgaris. We determine DNA binding and promoter activity by the HigB-HigA complex supported by structural biology and molecular dynamics simulations of an elusive DNA operator-TA repressor complex. To define the optimal oligomeric TA repressor-DNA operator complex required for derepression, we engineered a dedicated trimeric HigB-HigA2 complex that represses transcription more than 26-fold as compared to the tetrameric HigB2-HigA2. These results expand the known diversity of how the HigB-HigA TA family is autoregulated.