Structural and Functional Insights into Bacillus subtilis Sigma Factor Inhibitor, CsfB

Santiago Martínez-Lumbreras,Caterina Alfano,Nicola J Evans,Katherine M Collins,Kelly A Flanagan,R Andrew Atkinson,Ewelina M Krysztofinska,Anupama Vydyanath,Jacquelin Jackter,Sarah Fixon-Owoo,Amy H Camp,Rivka L Isaacson

doi:10.1016/j.str.2018.02.007

Santiago Martínez-Lumbreras, Caterina Alfano + Show 10 more

Open Access

https://doi.org/10.1016/j.str.2018.02.007

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Journal: Structure	Publication Date: Mar 8, 2018
Citations: 12	License type: cc-by

Affiliation: King's College London, Mount Holyoke College

Abstract

SummaryGlobal changes in bacterial gene expression can be orchestrated by the coordinated activation/deactivation of alternative sigma (σ) factor subunits of RNA polymerase. Sigma factors themselves are regulated in myriad ways, including via anti-sigma factors. Here, we have determined the solution structure of anti-sigma factor CsfB, responsible for inhibition of two alternative sigma factors, σG and σE, during spore formation by Bacillus subtilis. CsfB assembles into a symmetrical homodimer, with each monomer bound to a single Zn2+ ion via a treble-clef zinc finger fold. Directed mutagenesis indicates that dimer formation is critical for CsfB-mediated inhibition of both σG and σE, and we have characterized these interactions in vitro. This work represents an advance in our understanding of how CsfB mediates inhibition of two alternative sigma factors to drive developmental gene expression in a bacterium.

Highlights

Eukaryotic and prokaryotic cells alike possess the ability to alter their phenotypes through global changes in gene expression
One common mechanism bacteria utilize to effect large-scale changes in gene expression is through alternative sigma (s) factor subunits of RNA polymerase (RNAP)
All bacteria employ an essential primary sigma factor that directs transcription of housekeeping genes; many bacteria possess alternative sigma factors that compete for binding to RNAP and redirect it to transcribe sets of genes required for adaptive responses

Summary

Introduction

Eukaryotic and prokaryotic cells alike possess the ability to alter their phenotypes through global changes in gene expression. In bacteria, these transitions enable survival during stress conditions, drive developmental programs, and promote infection of host organisms. One common mechanism bacteria utilize to effect large-scale changes in gene expression is through alternative sigma (s) factor subunits of RNA polymerase (RNAP). The dissociable RNAP sigma factor subunit is responsible for recognition of promoter DNA and the subsequent initiation of transcription. Most sigma factors are members of the s70 superfamily, which is subdivided into four classes based upon conservation and the presence/absence of the conserved sigma domains (s1.1, s2, s3, and s4) that mediate interactions with RNAP and/or promoter DNA (reviewed in Feklistov et al, 2014; Paget, 2015). The suite of genes expressed in a bacterial cell can be reprogrammed by manipulating the levels, activity, or availability of alternative sigma factors (reviewed in Osterberg et al, 2011)

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