H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing
Type
ArticleAuthors
Shahul Hameed, Umar FLiao, Chenyi
Radhakrishnan, Anand K
Huser, Franceline
Aljedani, Safia Salim Eid
Zhao, Xiaochuan
Momin, Afaque Ahmad Imtiyaz

Melo, Fernando A
Guo, Xianrong
Brooks, Claire
Li, Yu
Cui, Xuefeng
Gao, Xin

Ladbury, John E
Jaremko, Lukasz

Jaremko, Mariusz

Li, Jianing
Arold, Stefan T.

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Computer Science
Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Imaging and Characterization Core Lab
NMR
Structural Biology and Engineering
Structural and Functional Bioinformatics Group
KAUST Grant Number
URF/1/1976-06URF/1/1976-04
3007
Date
2018-12-28Online Publication Date
2018-12-28Print Publication Date
2019-03-18Permanent link to this record
http://hdl.handle.net/10754/630773
Metadata
Show full item recordAbstract
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.Citation
Shahul Hameed UF, Liao C, Radhakrishnan AK, Huser F, Aljedani SS, et al. (2018) H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing. Nucleic Acids Research. Available: http://dx.doi.org/10.1093/nar/gky1299.Sponsors
ACKNOWLEDGEMENTS: We thank the Berkeley Laboratory Advanced Light Source and SIBYLS beamline staff at 12.3.1 for assistance with collection of SAXS data, and K. Dyer for the mail-in service provided by SIBYLS. We acknowledge SOLEIL for provision of synchrotron radiation facilities and we would like to thank J. Perez and A. Thureau for assistance in using the beamline SWING. We thank the KAUST Bioscience and Imaging core labs for their assistance. Computational resources were provided to J.L. by Vermont Advanced Computing Core (VACC), XSEDE (NSF Grant No. ACI-1053575) and PSC Anton (MMBioS through NIH Grant P41GM103712-S1). This research also used the resources of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST). FUNDING: The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]; King Abdullah University of Science and Technology (KAUST) through the baseline fund and the Office of Sponsored Research (OSR) [URF/1/1976-06, URF/1/1976-04 and 3007]. C.L. and J.L. were partially supported by the National Institutes of Health of USA [1R01GM129431-01]. Funding for open access charge: King Abdullah University of Science and Technology (KAUST).Publisher
Oxford University Press (OUP)Journal
Nucleic Acids Researchae974a485f413a2113503eed53cd6c53
10.1093/nar/gky1299
Scopus Count
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Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Imaging and Characterization Core Lab; Structural and Functional Bioinformatics Group; Computer Science Program; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
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