Artículo

Rinaldi, J.; Arrar, M.; Sycz, G.; Cerutti, M.L.; Berguer, P.M.; Paris, G.; Estrín, D.A.; Martí, M.A.; Klinke, S.; Goldbaum, F.A. "Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain" (2016) Journal of Molecular Biology. 428(6):1165-1179
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Abstract:

In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. © 2016 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain
Autor:Rinaldi, J.; Arrar, M.; Sycz, G.; Cerutti, M.L.; Berguer, P.M.; Paris, G.; Estrín, D.A.; Martí, M.A.; Klinke, S.; Goldbaum, F.A.
Filiación:Fundación Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, C1405BWE, Argentina
Departamento de Química Inorgánica, Analítica y Química Física e INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina
Plataforma Argentina de Biología Estructural y Metabolómica PLABEM, Avenida Patricias Argentinas 435, Buenos Aires, C1405BWE, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina
Centro de Investigaciones en Bionanociencias, CIBION-CONICET, Godoy Cruz 2390, Buenos Aires, C1425FQD, Argentina
Palabras clave:autophosphorylation mechanism; molecular dynamics simulations; signal transduction; two-component system; X-ray crystallography; dimer; homodimer; protein histidine kinase; protein kinase; protein-histidine kinase; Article; autophosphorylation; blue light; Brucella; conformation; cross linking; crystal structure; crystallography; dimerization; enzyme activity; enzyme structure; molecular dynamics; mutational analysis; nonhuman; priority journal; protein domain; protein family; chemistry; dna mutational analysis; enzymology; genetics; metabolism; phosphorylation; protein conformation; protein multimerization; protein processing; X ray crystallography; Brucella; Crystallography, X-Ray; DNA Mutational Analysis; Molecular Dynamics Simulation; Phosphorylation; Protein Conformation; Protein Kinases; Protein Multimerization; Protein Processing, Post-Translational
Año:2016
Volumen:428
Número:6
Página de inicio:1165
Página de fin:1179
DOI: http://dx.doi.org/10.1016/j.jmb.2016.01.026
Título revista:Journal of Molecular Biology
Título revista abreviado:J. Mol. Biol.
ISSN:00222836
CODEN:JMOBA
CAS:protein histidine kinase, 99283-67-7; protein kinase, 9026-43-1; Protein Kinases; protein-histidine kinase
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222836_v428_n6_p1165_Rinaldi

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Citas:

---------- APA ----------
Rinaldi, J., Arrar, M., Sycz, G., Cerutti, M.L., Berguer, P.M., Paris, G., Estrín, D.A.,..., Goldbaum, F.A. (2016) . Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain. Journal of Molecular Biology, 428(6), 1165-1179.
http://dx.doi.org/10.1016/j.jmb.2016.01.026
---------- CHICAGO ----------
Rinaldi, J., Arrar, M., Sycz, G., Cerutti, M.L., Berguer, P.M., Paris, G., et al. "Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain" . Journal of Molecular Biology 428, no. 6 (2016) : 1165-1179.
http://dx.doi.org/10.1016/j.jmb.2016.01.026
---------- MLA ----------
Rinaldi, J., Arrar, M., Sycz, G., Cerutti, M.L., Berguer, P.M., Paris, G., et al. "Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain" . Journal of Molecular Biology, vol. 428, no. 6, 2016, pp. 1165-1179.
http://dx.doi.org/10.1016/j.jmb.2016.01.026
---------- VANCOUVER ----------
Rinaldi, J., Arrar, M., Sycz, G., Cerutti, M.L., Berguer, P.M., Paris, G., et al. Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain. J. Mol. Biol. 2016;428(6):1165-1179.
http://dx.doi.org/10.1016/j.jmb.2016.01.026