Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB

ABSTRACT RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379–405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204–209, 2010, https://doi.org/10.1016/j.mib.2010.01...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ekaterina V. Filippova, Bozena Zemaitaitis, Theint Aung, Alan J. Wolfe, Wayne F. Anderson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	DNA-binding proteins transcription two-component signal transduction X-ray crystallography Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f361890557174f94b6a7f3106a8fd11c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f361890557174f94b6a7f3106a8fd11c
record_format	dspace
spelling	oai:doaj.org-article:f361890557174f94b6a7f3106a8fd11c2021-11-15T15:53:26ZStructural Basis for DNA Recognition by the Two-Component Response Regulator RcsB10.1128/mBio.01993-172150-7511https://doaj.org/article/f361890557174f94b6a7f3106a8fd11c2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01993-17https://doaj.org/toc/2150-7511ABSTRACT RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379–405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204–209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173–1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6–17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae, which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family Enterobacteriaceae.Ekaterina V. FilippovaBozena ZemaitaitisTheint AungAlan J. WolfeWayne F. AndersonAmerican Society for MicrobiologyarticleDNA-binding proteinstranscriptiontwo-component signal transductionX-ray crystallographyMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA-binding proteins transcription two-component signal transduction X-ray crystallography Microbiology QR1-502
spellingShingle	DNA-binding proteins transcription two-component signal transduction X-ray crystallography Microbiology QR1-502 Ekaterina V. Filippova Bozena Zemaitaitis Theint Aung Alan J. Wolfe Wayne F. Anderson Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
description	ABSTRACT RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379–405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204–209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173–1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6–17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae, which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family Enterobacteriaceae.
format	article
author	Ekaterina V. Filippova Bozena Zemaitaitis Theint Aung Alan J. Wolfe Wayne F. Anderson
author_facet	Ekaterina V. Filippova Bozena Zemaitaitis Theint Aung Alan J. Wolfe Wayne F. Anderson
author_sort	Ekaterina V. Filippova
title	Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
title_short	Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
title_full	Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
title_fullStr	Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
title_full_unstemmed	Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
title_sort	structural basis for dna recognition by the two-component response regulator rcsb
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/f361890557174f94b6a7f3106a8fd11c
work_keys_str_mv	AT ekaterinavfilippova structuralbasisfordnarecognitionbythetwocomponentresponseregulatorrcsb AT bozenazemaitaitis structuralbasisfordnarecognitionbythetwocomponentresponseregulatorrcsb AT theintaung structuralbasisfordnarecognitionbythetwocomponentresponseregulatorrcsb AT alanjwolfe structuralbasisfordnarecognitionbythetwocomponentresponseregulatorrcsb AT waynefanderson structuralbasisfordnarecognitionbythetwocomponentresponseregulatorrcsb
_version_	1718427314263425024

Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB

Ejemplares similares