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Abstract:

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.

Registro:

Documento: Artículo
Título:Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action
Autor:Trajtenberg, F.; Imelio, J.A.; Machado, M.R.; Larrieux, N.; Marti, M.A.; Obal, G.; Mechaly, A.E.; Buschiazzo, A.
Filiación:Laboratory of Molecular and Structural Microbiology, Institut Pasteur de Montevideo, Montevideo, Uruguay
Biomolecular Simulations, Institut Pasteur de Montevideo, Montevideo, Uruguay
Departamento de Química Biológica e IQUIBICEN-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Protein Biophysics Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay
Département de Microbiologie, Institut Pasteur, Paris, France
Molecular Mechanisms of Membrane Transport, Institut Pasteur, Paris, France
Palabras clave: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
Año:2016
Volumen:5
Número:DECEMBER2016
DOI: http://dx.doi.org/10.7554/eLife.21422
Título revista:eLife
Título revista abreviado:eLife
ISSN:2050084X
CAS:phosphatase, 9013-05-2; phosphotransferase, 9031-09-8, 9031-44-1; protein histidine kinase, 99283-67-7; Histidine Kinase; Transcription Factors
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_2050084X_v5_nDECEMBER2016_p_Trajtenberg

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Citas:

---------- APA ----------
Trajtenberg, F., Imelio, J.A., Machado, M.R., Larrieux, N., Marti, M.A., Obal, G., Mechaly, A.E.,..., Buschiazzo, A. (2016) . Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action. eLife, 5(DECEMBER2016).
http://dx.doi.org/10.7554/eLife.21422
---------- CHICAGO ----------
Trajtenberg, F., Imelio, J.A., Machado, M.R., Larrieux, N., Marti, M.A., Obal, G., et al. "Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action" . eLife 5, no. DECEMBER2016 (2016).
http://dx.doi.org/10.7554/eLife.21422
---------- MLA ----------
Trajtenberg, F., Imelio, J.A., Machado, M.R., Larrieux, N., Marti, M.A., Obal, G., et al. "Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action" . eLife, vol. 5, no. DECEMBER2016, 2016.
http://dx.doi.org/10.7554/eLife.21422
---------- VANCOUVER ----------
Trajtenberg, F., Imelio, J.A., Machado, M.R., Larrieux, N., Marti, M.A., Obal, G., et al. Regulation of signaling directionality revealed by 3D snapshots of a kinase: Regulator complex in action. eLife. 2016;5(DECEMBER2016).
http://dx.doi.org/10.7554/eLife.21422