Interaction of a partially disordered antisigma factor with its partner, the signaling domain of the TonB-dependent transporter HasR.

Idir Malki,Catherine Simenel,Gisele Cardoso De Amorim,Halina Wojtowicz,Alain Chaffotte,Patrick England,Ada Prochnicka-Chalufour,Nadia Izadi-Pruneyre,Sylviane Hoos,Philippe Delepelaire,Bertrand Raynal,Muriel Delepierre

doi:10.1371/journal.pone.0089502

Abstract

Bacteria use diverse signaling pathways to control gene expression in response to external stimuli. In Gram-negative bacteria, the binding of a nutrient is sensed by an outer membrane transporter. This signal is then transmitted to an antisigma factor and subsequently to the cytoplasm where an ECF sigma factor induces expression of genes related to the acquisition of this nutrient. The molecular interactions involved in this transmembrane signaling are poorly understood and structural data on this family of antisigma factor are rare. Here, we present the first structural study of the periplasmic domain of an antisigma factor and its interaction with the transporter. The study concerns the signaling in the heme acquisition system (Has) of Serratia marcescens. Our data support unprecedented partially disordered periplasmic domain of an anti-sigma factor HasS in contact with a membrane-mimicking environment. We solved the 3D structure of the signaling domain of HasR transporter and identified the residues at the HasS−HasR interface. Their conservation in several bacteria suggests wider significance of the proposed model for the understanding of bacterial transmembrane signaling.

Highlights

Bacteria need external sensors and signaling processes that enable them to detect environmental changes and to respond by differential gene expression
On the basis of bioinformatic analysis of this family of antisigma factor and in vivo studies of the Fec system, we have defined three different C-terminal domains of HasS: an entire periplasmic domain, HasS102 corresponding to the region downstream from the putative transmembrane helix, HasS166 containing residues 166 to 317 starting after a stretch rich in hydrophobic residues and predicted as an additional putative transmembrane fragment, and HasSCTD corresponding to the last 78 residues
HasSCTD is similar to the shortest domain of FecR, the most studied antisigma factor of this family, defined as the domain of interaction with the transporter [12]

Summary

Introduction

Bacteria need external sensors and signaling processes that enable them to detect environmental changes (light, oxidative stress, availability of some nutrients, etc) and to respond by differential gene expression. These specific genes are regulated by a class of sigma factors named ECF sigma factors (for ExtraCytoplasmic Function) [1]. The antisigma factor becomes inactive, either by degradation through a cascade of regulated proteolytic steps, or through conformational changes [2,3] Both mechanisms result in release and consequent activation of the ECF sigma factor, which can induce gene expression of its target promoters [1]

Methods

Results

Conclusion