Structural Underpinnings of Nitrogen Regulation by the Prototypical Nitrogen-Responsive Transcriptional Factor NrpR

Goragot Wisedchaisri, David M. Dranow, Thomas J. Lie, Jeffrey B. Bonanno, Yury Patskovsky, Sinem A. Ozyurt, J. Michael Sauder, Steven C. Almo, Stephen R. Wasserman, Stephen K. Burley, John A. Leigh, Tamir Gonen

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Plants and microorganisms reduce environmental inorganic nitrogen to ammonium, which then enters various metabolic pathways solely via conversion of 2-oxoglutarate (2OG) to glutamate and glutamine. Cellular 2OG concentrations increase during nitrogen starvation. We recently identified a family of 2OG-sensing proteins-the nitrogen regulatory protein NrpR-that bind DNA and repress transcription of nitrogen assimilation genes. We used X-ray crystallography to determine the structure of NrpR regulatory domain. We identified the NrpR 2OG-binding cleft and show that residues predicted to interact directly with 2OG are conserved among diverse classes of 2OG-binding proteins. We show that high levels of 2OG inhibit NrpRs ability to bind DNA. Electron microscopy analyses document that NrpR adopts different quaternary structures in its inhibited 2OG-bound state compared with its active apo state. Our results indicate that upon 2OG release, NrpR repositions its DNA-binding domains correctly for optimal interaction with DNA thereby enabling gene repression.

Original languageEnglish (US)
Pages (from-to)1512-1521
Number of pages10
JournalStructure
Volume18
Issue number11
DOIs
StatePublished - Nov 10 2010

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Wisedchaisri, G., Dranow, D. M., Lie, T. J., Bonanno, J. B., Patskovsky, Y., Ozyurt, S. A., Sauder, J. M., Almo, S. C., Wasserman, S. R., Burley, S. K., Leigh, J. A., & Gonen, T. (2010). Structural Underpinnings of Nitrogen Regulation by the Prototypical Nitrogen-Responsive Transcriptional Factor NrpR. Structure, 18(11), 1512-1521. https://doi.org/10.1016/j.str.2010.08.014