The fused SnoaL_2 domain in the Mycobacterium tuberculosis sigma factor σ(J) modulates promoter recognition

Extra-cytoplasmic function (ECF) σ-factors are widespread in bacteria, linking environmental stimuli with changes in gene expression. These transcription factors span several phylogenetically distinct groups and are remarkably diverse in their activation and regulatory mechanisms. Here, we describe the structural and biochemical features of a Mycobacterium tuberculosis ECF factor σ(J) that suggests that the SnoaL_2 domain at the C-terminus can modulate the activity of this initiation factor in the absence of a cognate regulatory anti-σ factor. M. tuberculosis σ(J) can bind promoter DNA in vitro; this interaction is substantially impaired by the removal of the SnoaL_2 domain. This finding is consistent with assays to evaluate σ(J)-mediated gene expression. Structural similarity of the SnoaL_2 domain with epoxide hydrolases also suggests a novel functional role for this domain. The conserved sequence features between M. tuberculosis σ(J) and other members of the ECF41 family of σ-factors suggest that the regulatory mechanism involving the C-terminal SnoaL_2 domain is likely to be retained in this family of proteins. These studies suggest that the ECF41 family of σ-factors incorporate features of both—the σ(70) family and bacterial one—component systems thereby providing a direct mechanism to implement environment-mediated transcription changes.