Structure and functional implications of WYL domain-containing bacterial DNA damage response regulator PafBC

Nat Commun. 2019 Oct 11;10(1):4653. doi: 10.1038/s41467-019-12567-x.


In mycobacteria, transcriptional activator PafBC is responsible for upregulating the majority of genes induced by DNA damage. Understanding the mechanism of PafBC activation is impeded by a lack of structural information on this transcription factor that contains a widespread, but poorly understood WYL domain frequently encountered in bacterial transcription factors. Here, we determine the crystal structure of Arthrobacter aurescens PafBC. The protein consists of two modules, each harboring an N-terminal helix-turn-helix DNA-binding domain followed by a central WYL and a C-terminal extension (WCX) domain. The WYL domains exhibit Sm-folds, while the WCX domains adopt ferredoxin-like folds, both characteristic for RNA-binding proteins. Our results suggest a mechanism of regulation in which WYL domain-containing transcription factors may be activated by binding RNA or other nucleic acid molecules. Using an in vivo mutational screen in Mycobacterium smegmatis, we identify potential co-activator binding sites on PafBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology
  • Crystallography, X-Ray
  • DNA Damage*
  • Gene Expression Regulation, Bacterial
  • Micrococcaceae / genetics*
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Up-Regulation


  • Bacterial Proteins
  • Transcription Factors

Supplementary concepts

  • Paenarthrobacter aurescens