Reference

portadaARSAntioxid Redox Signal. 2016 Feb 1; 24(4): 173–185. doi:10.1089/ars.2014.6175

Authors

Botello-Morte Laura, Pellicer Silvia, Sein-Echaluce Violeta C., Contreras Lellys M., Neira José Luis, Abián Olga, Velázquez-Campoy Adrián, Peleato María Luisa, Fillat María F., and Bes María Teresa

Abstract

BACKGROUND:
Aims: The ferric uptake regulator (Fur) is the main transcriptional regulator of genes involved in iron homeostasis in most prokaryotes. FurA from Anabaena sp. PCC 7120 contains five cysteine residues, four of them arranged in two redox-active CXXC motifs. The protein needs not only metal but also reducing conditions to remain fully active in vitro. Through a mutational study of the cysteine residues present in FurA, we have investigated their involvement in metal and DNA binding. Results: Residue C101 that belongs to a conserved CXXC motif plays an essential role in both metal and DNA binding activities in vitro. Substitution of C101 by serine impairs DNA and metal binding abilities of FurA. Isothermal titration calorimetry measurements show that the redox state of C101 is responsible for the protein ability to coordinate the metal corepressor. Moreover, the redox state of C101 varies with the presence or absence of C104 or C133, suggesting that the environments of these cysteines are mutually interdependent. Innovation: We propose that C101 is part of a thiol/disulfide redox switch that determines FurA ability to bind the metal corepressor. Conclusion: This mechanism supports a novel feature of a Fur protein that emerges as a regulator, which connects the response to changes in the intracellular redox state and iron management in cyanobacteria.

Description

Este trabajo propone un nuevo mecanismo de acción para el regulador global FurA, que en ciertas condiciones puede actuar como un sensor redox basado en sus motivos CXXC para modular su actividad transcripcional. La Cys101, esencial para unión al DNA y al metal correpresor, parece ser responsable de la dimerización de FurA en solución. Además, la Cys104 constituye junto con la Cys101 o la Cys133 un interruptor redox que coordina el estado redox y la actividad del regulador.

 

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REFERENCIA DEL GRUPO INVESTIGADOR

El grupo "Regulación génica y fisiología de cianobacterias" (BIFI – Universidad de Zaragoza) investiga la regulación del metabolismo del hierro y su relación con el metabolismo nitrogenado, los mecanismos de defensa el estrés oxidativo y la producción de cianotoxinas. Actualmente nuestro trabajo está centrado en la caracterización funcional de la superfamilia de reguladores FUR (ferric uptake regulator) en cianobacterias y diversos patógenos de interés clínico y ambiental.

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