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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)2666-2680
Number of pages15
JournalNucleic Acids Research
Issue number5
StatePublished - Dec 28 2018


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