H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing.

Umar F Shahul Hameed,Xiaochuan Zhao,Mariusz Jaremko,Chenyi Liao,Claire Brooks,Anand K Radhakrishnan,John E Ladbury,Afaque A Momin,Fernando A Melo,Xianrong Guo,Stefan T Arold,Łukasz Jaremko,Yu Li,Jianing Li,Safia S Aljedani,Xuefeng Cui,Xin Gao,Franceline Huser

doi:10.1093/nar/gky1299

Abstract

As an environment-dependent pleiotropic gene regulator in Gram-negative bacteria, the H-NS protein is crucial for adaptation and toxicity control of human pathogens such as Salmonella, Vibrio cholerae or enterohaemorrhagic Escherichia coli. Changes in temperature affect the capacity of H-NS to form multimers that condense DNA and restrict gene expression. However, the molecular mechanism through which H-NS senses temperature and other physiochemical parameters remains unclear and controversial. Combining structural, biophysical and computational analyses, we show that human body temperature promotes unfolding of the central dimerization domain, breaking up H-NS multimers. This unfolding event enables an autoinhibitory compact H-NS conformation that blocks DNA binding. Our integrative approach provides the molecular basis for H-NS–mediated environment-sensing and may open new avenues for the control of pathogenic multi-drug resistant bacteria.

Highlights

By controlling the expression of >200 genes in an environment-dependent manner, the histone-like nucleoidstructuring (H-NS) protein contributes crucially to the fitness of enterobacteria, including pathogenic and multidrug resistant strains [1,2,3,4]
Dm and Rg values were in agreement with those calculated for the antiparallel H-NS2–57,C21S model (Dm = 75 A ; Rg = 19.4 A ), but not with those of the parallel structure (Dm = 58 A ; Rg = 18.5 A )
The experimental small angle X-ray scattering (SAXS) patterns for all conditions fitted the SAXS pattern calculated for the antiparallel site1 dimer significantly better than those calculated for the parallel model [␹ 2T = 10◦C: 2.22; 7.56

Summary

Introduction

By controlling the expression of >200 genes in an environment-dependent manner, the histone-like nucleoidstructuring (H-NS) protein contributes crucially to the fitness of enterobacteria, including pathogenic and multidrug resistant strains [1,2,3,4]. H-NS releases DNA to enable gene expression, depending on the growth phase, and in response to changes in environmental factors, such as temperature, osmolarity and pH [4,19,20,21]. This mechanism is thought to allow bacteria to sense their presence within a warm-blooded host and adapt the bacteria’s response .

Methods

Results

Conclusion