H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing
AuthorsShahul Hameed, Umar F
Radhakrishnan, Anand K
Aljedani, Safia Salim Eid
Momin, Afaque Ahmad Imtiyaz
Melo, Fernando A
Ladbury, John E
Arold, Stefan T.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Imaging and Characterization Core Lab
Structural Biology and Engineering
Structural and Functional Bioinformatics Group
Online Publication Date2018-12-28
Print Publication Date2019-03-18
Permanent link to this recordhttp://hdl.handle.net/10754/630773
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AbstractAs 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.
CitationShahul 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.
SponsorsACKNOWLEDGEMENTS: 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).
PublisherOxford University Press (OUP)
JournalNucleic Acids Research
CollectionsArticles; Biological and Environmental Sciences 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 Sciences and Engineering (CEMSE) Division
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