Structural determinants of DNA recognition by the NO sensor NsrR and related Rrf2-type [FeS]-transcription factors

Rohac, Roman, Crack, Jason C., de Rosny, Eve, Gigarel, Océane, Le Brun, Nick E. ORCID:, Fontecilla-Camps, Juan C. and Volbeda, Anne (2022) Structural determinants of DNA recognition by the NO sensor NsrR and related Rrf2-type [FeS]-transcription factors. Communications Biology, 5. ISSN 2399-3642

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Several transcription factors of the Rrf2 family use an iron-sulfur cluster to regulate DNA binding through effectors such as nitric oxide (NO), cellular redox status and iron levels. [4Fe-4S]-NsrR from Streptomyces coelicolor (ScNsrR) modulates expression of three different genes via reaction and complex formation with variable amounts of NO, which results in detoxification of this gas. Here, we report the crystal structure of ScNsrR complexed with an hmpA1 gene operator fragment and compare it with those previously reported for [2Fe-2S]-RsrR/rsrR and apo-IscR/hyA complexes. Important structural differences reside in the variation of the DNA minor and major groove widths. In addition, different DNA curvatures and different interactions with the protein sensors are observed. We also report studies of NsrR binding to four hmpA1 variants, which indicate that flexibility in the central region is not a key binding determinant. Our study explores the promotor binding specificities of three closely related transcriptional regulators.

Item Type: Article
Additional Information: Acknowledgements: The authors thank Christophe Caillat for collecting the first ScNsrR/hmpA1 complex X-ray diffraction data set at the SOLEIL synchrotron. We acknowledge the Paul Scherrer Institut, Villigen, Switzerland for provision of synchrotron radiation beamtime at beamline X06SA of the SLS and thank Ezequiel Panepucci for assistance with data collection. This work was supported by the Agence Nationale de la Recherche [ANR-18-CE11-0010 (MANGO- ICING) and ANR-10-INSB-05-02 (FRISBI, within the Grenoble Partnership for Structural Biology)], the European Union’s Horizon 2020 Research and Innovation programme [grant agreement nr. 730872 (CALIPSOplus)] and the Biotechnology and Biological Sciences Research Council [BB/P006140/1]. Funding for open charge access: [ANR-18-CE11-0010].
Uncontrolled Keywords: medicine (miscellaneous),biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all) ,/dk/atira/pure/subjectarea/asjc/2700/2701
Faculty \ School: Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Groups > Chemistry of Life Processes
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
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Depositing User: LivePure Connector
Date Deposited: 27 Jul 2022 10:31
Last Modified: 23 Oct 2022 04:06
DOI: 10.1038/s42003-022-03745-7


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