H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1093/nar/gky1299 http://hdl.handle.net/11449/185714 |
Resumo: | 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. |
id |
UNSP_15a114fbae916d0bf371df86992d94f9 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/185714 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencingAs 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.Office of Science, Office of Basic Energy Sciences, of the U.S. Department of EnergyOffice of Sponsored Research (OSR)National Institutes of Health of USAKing Abdullah University of Science and Technology (KAUST)King Abdullah Univ Sci & Technol, Div Biol & Environm Sci & Engn BESE, Computat Biosci Res Ctr, Thuwal 239556900, Saudi ArabiaUniv Vermont, Dept Chem, Burlington, VT 05405 USASao Paulo State Univ, Dept Phys IBILCE, Sao Paulo, BrazilKing Abdullah Univ Sci & Technol, Imaging & Characterizat Core Lab, Thuwal 239556900, Saudi ArabiaKing Abdullah Univ Sci & Technol, Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div BESE, Thuwal 239556900, Saudi ArabiaUniv Leeds, Sch Mol & Cellular Biol, Leeds, W Yorkshire, EnglandKing Abdullah Univ Sci & Technol, Div Biol & Environm Sci & Engn, Thuwal 239556900, Saudi ArabiaSao Paulo State Univ, Dept Phys IBILCE, Sao Paulo, BrazilOffice of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy: DE-AC02-05CH11231Office of Sponsored Research (OSR): URF/1/1976-06Office of Sponsored Research (OSR): URF/1/1976-04Office of Sponsored Research (OSR): 3007National Institutes of Health of USA: 1R01GM129431-01Oxford Univ PressKing Abdullah Univ Sci & TechnolUniv VermontUniversidade Estadual Paulista (Unesp)Univ LeedsHameed, Umar F. ShahulLiao, ChenyiRadhakrishnan, Anand K.Huser, FrancelineAljedani, Safia S.Zhao, XiaochuanMomin, Afaque A.Melo, Fernando A. [UNESP]Guo, XianrongBrooks, ClaireLi, YuCui, XuefengGao, XinLadbury, John E.Jaremko, LukaszJaremko, MariuszLi, JianingArold, Stefan T.2019-10-04T12:37:55Z2019-10-04T12:37:55Z2019-03-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2666-2680http://dx.doi.org/10.1093/nar/gky1299Nucleic Acids Research. Oxford: Oxford Univ Press, v. 47, n. 5, p. 2666-2680, 2019.0305-1048http://hdl.handle.net/11449/18571410.1093/nar/gky1299WOS:000467963700045Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNucleic Acids Researchinfo:eu-repo/semantics/openAccess2021-10-23T05:43:36Zoai:repositorio.unesp.br:11449/185714Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:24:53.797318Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
title |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
spellingShingle |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing Hameed, Umar F. Shahul |
title_short |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
title_full |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
title_fullStr |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
title_full_unstemmed |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
title_sort |
H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing |
author |
Hameed, Umar F. Shahul |
author_facet |
Hameed, Umar F. Shahul Liao, Chenyi Radhakrishnan, Anand K. Huser, Franceline Aljedani, Safia S. Zhao, Xiaochuan Momin, Afaque A. Melo, Fernando A. [UNESP] Guo, Xianrong Brooks, Claire Li, Yu Cui, Xuefeng Gao, Xin Ladbury, John E. Jaremko, Lukasz Jaremko, Mariusz Li, Jianing Arold, Stefan T. |
author_role |
author |
author2 |
Liao, Chenyi Radhakrishnan, Anand K. Huser, Franceline Aljedani, Safia S. Zhao, Xiaochuan Momin, Afaque A. Melo, Fernando A. [UNESP] Guo, Xianrong Brooks, Claire Li, Yu Cui, Xuefeng Gao, Xin Ladbury, John E. Jaremko, Lukasz Jaremko, Mariusz Li, Jianing Arold, Stefan T. |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
King Abdullah Univ Sci & Technol Univ Vermont Universidade Estadual Paulista (Unesp) Univ Leeds |
dc.contributor.author.fl_str_mv |
Hameed, Umar F. Shahul Liao, Chenyi Radhakrishnan, Anand K. Huser, Franceline Aljedani, Safia S. Zhao, Xiaochuan Momin, Afaque A. Melo, Fernando A. [UNESP] Guo, Xianrong Brooks, Claire Li, Yu Cui, Xuefeng Gao, Xin Ladbury, John E. Jaremko, Lukasz Jaremko, Mariusz Li, Jianing Arold, Stefan T. |
description |
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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-04T12:37:55Z 2019-10-04T12:37:55Z 2019-03-18 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1093/nar/gky1299 Nucleic Acids Research. Oxford: Oxford Univ Press, v. 47, n. 5, p. 2666-2680, 2019. 0305-1048 http://hdl.handle.net/11449/185714 10.1093/nar/gky1299 WOS:000467963700045 |
url |
http://dx.doi.org/10.1093/nar/gky1299 http://hdl.handle.net/11449/185714 |
identifier_str_mv |
Nucleic Acids Research. Oxford: Oxford Univ Press, v. 47, n. 5, p. 2666-2680, 2019. 0305-1048 10.1093/nar/gky1299 WOS:000467963700045 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nucleic Acids Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
2666-2680 |
dc.publisher.none.fl_str_mv |
Oxford Univ Press |
publisher.none.fl_str_mv |
Oxford Univ Press |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128646251020288 |