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

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

doi:10.1093/nar/gky1299

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2666-2680
Number of pages	15
Journal	Nucleic acids research
Volume	47
Issue number	5
DOIs	https://doi.org/10.1093/nar/gky1299
State	Published - Mar 18 2019

Bibliographical note

Funding Information:
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 Abdul-lah University of Science & Technology (KAUST).

Funding Information:
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). Conflict of interest statement. None declared.

Publisher Copyright:
© The Author(s) 2018.

ASJC Scopus subject areas

Genetics

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10.1093/nar/gky1299

Cite this

Hameed, U. F. S., Liao, C., Radhakrishnan, A. K., Huser, F., Aljedani, S. S., Zhao, X., Momin, A. A., Melo, F. A., Guo, X., Brooks, C., Li, Y., Cui, X., Gao, X., Ladbury, J. E., Jaremko, Ł., Jaremko, M., Li, J., & Arold, S. T. (2019). H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing. Nucleic acids research, 47(5), 2666-2680. https://doi.org/10.1093/nar/gky1299

@article{691782e0bad14b15a5f398b671a4abd7,

title = "H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing",

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.",

author = "Hameed, {Umar F.Shahul} and Chenyi Liao and Radhakrishnan, {Anand K.} and Franceline Huser and Aljedani, {Safia S.} and Xiaochuan Zhao and Momin, {Afaque A.} and Melo, {Fernando A.} and Xianrong Guo and Claire Brooks and Yu Li and Xuefeng Cui and Xin Gao and Ladbury, {John E.} and {\L}ukasz Jaremko and Mariusz Jaremko and Jianing Li and Arold, {Stefan T.}",

note = "Funding Information: 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 Abdul-lah University of Science & Technology (KAUST). Funding Information: 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). Conflict of interest statement. None declared. Publisher Copyright: {\textcopyright} The Author(s) 2018.",

year = "2019",

month = mar,

day = "18",

doi = "10.1093/nar/gky1299",

language = "English (US)",

volume = "47",

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Hameed, UFS, Liao, C, Radhakrishnan, AK, Huser, F, Aljedani, SS, Zhao, X, Momin, AA, Melo, FA, Guo, X, Brooks, C, Li, Y, Cui, X, Gao, X, Ladbury, JE, Jaremko, Ł , Jaremko, M, Li, J & Arold, ST 2019, 'H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing', Nucleic acids research, vol. 47, no. 5, pp. 2666-2680. https://doi.org/10.1093/nar/gky1299

TY - JOUR

T1 - H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing

AU - Hameed, Umar F.Shahul

AU - Liao, Chenyi

AU - Radhakrishnan, Anand K.

AU - Huser, Franceline

AU - Aljedani, Safia S.

AU - Zhao, Xiaochuan

AU - Momin, Afaque A.

AU - Melo, Fernando A.

AU - Guo, Xianrong

AU - Brooks, Claire

AU - Li, Yu

AU - Cui, Xuefeng

AU - Gao, Xin

AU - Ladbury, John E.

AU - Jaremko, Łukasz

AU - Jaremko, Mariusz

AU - Li, Jianing

AU - Arold, Stefan T.

N1 - Funding Information: 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 Abdul-lah University of Science & Technology (KAUST). Funding Information: 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). Conflict of interest statement. None declared. Publisher Copyright: © The Author(s) 2018.

PY - 2019/3/18

Y1 - 2019/3/18

N2 - 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.

AB - 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.

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DO - 10.1093/nar/gky1299

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

Abstract

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