Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action

Two-component systems (TCS) are protein machineries that enable cells to respond to input signals. Histidine kinases (HK) are the sensory component, transferring information toward downstream response regulators (RR). HKs transfer phosphoryl groups to their specific RRs, but also dephosphorylate the...

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Autores principales:	Martí, Marcelo Adrián, Buschiazzo, Alejandro
Publicado:	2016
Materias:	phosphatase phosphotransferase protein histidine kinase transcription factor amino acid sequence Article Bacillus subtilis cloning computer model crystal structure crystallization entropy isothermal titration calorimetry molecular dynamics mutagenesis phosphate transport point mutation protein conformation protein dephosphorylation protein expression protein purification signal transduction size exclusion chromatography structure analysis three dimensional imaging X ray crystallography X ray diffraction chemistry enzymology metabolism molecular model phosphorylation protein processing Crystallography, X-Ray Histidine Kinase Models, Molecular Phosphorylation Protein Conformation Protein Processing, Post-Translational Signal Transduction Transcription Factors
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg http://hdl.handle.net/20.500.12110/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg
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spelling	paper:paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg2023-06-08T16:33:49Z Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action Martí, Marcelo Adrián Buschiazzo, Alejandro phosphatase phosphotransferase protein histidine kinase protein histidine kinase transcription factor amino acid sequence Article Bacillus subtilis cloning computer model crystal structure crystallization entropy isothermal titration calorimetry molecular dynamics mutagenesis phosphate transport point mutation protein conformation protein dephosphorylation protein expression protein purification signal transduction size exclusion chromatography structure analysis three dimensional imaging X ray crystallography X ray diffraction chemistry enzymology metabolism molecular model phosphorylation protein processing Bacillus subtilis Crystallography, X-Ray Histidine Kinase Models, Molecular Phosphorylation Protein Conformation Protein Processing, Post-Translational Signal Transduction Transcription Factors Two-component systems (TCS) are protein machineries that enable cells to respond to input signals. Histidine kinases (HK) are the sensory component, transferring information toward downstream response regulators (RR). HKs transfer phosphoryl groups to their specific RRs, but also dephosphorylate them, overall ensuring proper signaling. The mechanisms by which HKs discriminate between such disparate directions, are yet unknown. We now disclose crystal structures of the HK:RR complex DesK:DesR from Bacillus subtilis, comprising snapshots of the phosphotransfer and the dephosphorylation reactions. The HK dictates the reactional outcome through conformational rearrangements that include the reactive histidine. The phosphotransfer center is asymmetric, poised for dissociative nucleophilic substitution. The structural bases of HK phosphatase/phosphotransferase control are uncovered, and the unexpected discovery of a dissociative reactional center, sheds light on the evolution of TCS phosphotransfer reversibility. Our findings should be applicable to a broad range of signaling systems and instrumental in synthetic TCS rewiring. © Trajtenberg et al. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Buschiazzo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg http://hdl.handle.net/20.500.12110/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	phosphatase phosphotransferase protein histidine kinase protein histidine kinase transcription factor amino acid sequence Article Bacillus subtilis cloning computer model crystal structure crystallization entropy isothermal titration calorimetry molecular dynamics mutagenesis phosphate transport point mutation protein conformation protein dephosphorylation protein expression protein purification signal transduction size exclusion chromatography structure analysis three dimensional imaging X ray crystallography X ray diffraction chemistry enzymology metabolism molecular model phosphorylation protein processing Bacillus subtilis Crystallography, X-Ray Histidine Kinase Models, Molecular Phosphorylation Protein Conformation Protein Processing, Post-Translational Signal Transduction Transcription Factors
spellingShingle	phosphatase phosphotransferase protein histidine kinase protein histidine kinase transcription factor amino acid sequence Article Bacillus subtilis cloning computer model crystal structure crystallization entropy isothermal titration calorimetry molecular dynamics mutagenesis phosphate transport point mutation protein conformation protein dephosphorylation protein expression protein purification signal transduction size exclusion chromatography structure analysis three dimensional imaging X ray crystallography X ray diffraction chemistry enzymology metabolism molecular model phosphorylation protein processing Bacillus subtilis Crystallography, X-Ray Histidine Kinase Models, Molecular Phosphorylation Protein Conformation Protein Processing, Post-Translational Signal Transduction Transcription Factors Martí, Marcelo Adrián Buschiazzo, Alejandro Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
topic_facet	phosphatase phosphotransferase protein histidine kinase protein histidine kinase transcription factor amino acid sequence Article Bacillus subtilis cloning computer model crystal structure crystallization entropy isothermal titration calorimetry molecular dynamics mutagenesis phosphate transport point mutation protein conformation protein dephosphorylation protein expression protein purification signal transduction size exclusion chromatography structure analysis three dimensional imaging X ray crystallography X ray diffraction chemistry enzymology metabolism molecular model phosphorylation protein processing Bacillus subtilis Crystallography, X-Ray Histidine Kinase Models, Molecular Phosphorylation Protein Conformation Protein Processing, Post-Translational Signal Transduction Transcription Factors
description	Two-component systems (TCS) are protein machineries that enable cells to respond to input signals. Histidine kinases (HK) are the sensory component, transferring information toward downstream response regulators (RR). HKs transfer phosphoryl groups to their specific RRs, but also dephosphorylate them, overall ensuring proper signaling. The mechanisms by which HKs discriminate between such disparate directions, are yet unknown. We now disclose crystal structures of the HK:RR complex DesK:DesR from Bacillus subtilis, comprising snapshots of the phosphotransfer and the dephosphorylation reactions. The HK dictates the reactional outcome through conformational rearrangements that include the reactive histidine. The phosphotransfer center is asymmetric, poised for dissociative nucleophilic substitution. The structural bases of HK phosphatase/phosphotransferase control are uncovered, and the unexpected discovery of a dissociative reactional center, sheds light on the evolution of TCS phosphotransfer reversibility. Our findings should be applicable to a broad range of signaling systems and instrumental in synthetic TCS rewiring. © Trajtenberg et al.
author	Martí, Marcelo Adrián Buschiazzo, Alejandro
author_facet	Martí, Marcelo Adrián Buschiazzo, Alejandro
author_sort	Martí, Marcelo Adrián
title	Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
title_short	Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
title_full	Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
title_fullStr	Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
title_full_unstemmed	Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
title_sort	regulation of signaling directionality revealed by 3d snapshots of a kinase: regulator complex in action
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg http://hdl.handle.net/20.500.12110/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg
work_keys_str_mv	AT martimarceloadrian regulationofsignalingdirectionalityrevealedby3dsnapshotsofakinaseregulatorcomplexinaction AT buschiazzoalejandro regulationofsignalingdirectionalityrevealedby3dsnapshotsofakinaseregulatorcomplexinaction
_version_	1768544060769828864

Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action

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