CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis in Pyrococcus furiosus

Grünberger, Felix and Reichelt, Robert and Waege, Ingrid and Ned, Verena and Bronner, Korbinian and Kaljanac, Marcell and Weber, Nina and El Ahmad, Zubeir and Knauss, Lena and Madej, M. Gregor and Ziegler, Christine and Grohmann, Dina and Hausner, Winfried (2021) CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis in Pyrococcus furiosus. FRONTIERS IN MICROBIOLOGY, 11: 613532. ISSN 1664-302X

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Abstract

Although copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analyzed the transcriptome-wide response of Pyrococcus furiosus to increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process. To this end, we employed biochemical and biophysical methods to characterize the role of CopR. Additionally, a copR knockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 mu M copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the regulatory network that enables Pyrococcus to respond to increased copper concentrations.

Item Type: Article
Uncontrolled Keywords: METAL-BINDING DOMAIN; SULFOLOBUS-SOLFATARICUS; HYPERTHERMOPHILIC ARCHAEON; HYDROGEN-PEROXIDE; CRYSTAL-STRUCTURE; RNA-POLYMERASES; GENE-CLUSTER; OPEN COMPLEX; PROTEIN LRP; SS-LRPB; archaea; transcription; Pyrococcus; CopR; copper; regulation
Subjects: 500 Science > 540 Chemistry & allied sciences
500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler
Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie (Archaeenzentrum) > Prof. Dr. Dina Grohmann
Depositing User: Dr. Gernot Deinzer
Date Deposited: 01 Jun 2022 06:37
Last Modified: 01 Jun 2022 06:37
URI: https://pred.uni-regensburg.de/id/eprint/45577

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