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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Detalles Bibliográficos
Autores principales: Martí, Marcelo Adrián, Buschiazzo, Alejandro
Publicado: 2016
Materias:
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:
id paper:paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg
record_format dspace
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
bdutipo_str Repositorios
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