A Novel Mechanism of Coactivator Recruitment by the Nurr1 Nuclear Receptor

Nicolas Daffern, Ishwar Radhakrishnan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Nuclear receptors constitute one of the largest families of transcription factors that regulate genes in metazoans in response to small molecule ligands. Many receptors harbor two transactivation domains, one at each end of the protein sequence. Whereas the molecular mechanisms of transactivation mediated by the ligand-binding domain at the C-terminus of the protein are generally well established, the mechanism involving the N-terminal domain called activation function 1 (AF1) has remained elusive. Previous studies implicated the AF1 domain as a significant contributor towards the overall transcriptional activity of the NR4A family of nuclear receptors and suggested that the steroid receptor coactivators (SRCs) play an important role in this process. Here we show that a short segment within the AF1 domain of the NR4A receptor Nurr1 can directly engage with the SRC1 PAS-B domain. We also show that this segment forms a helix upon binding to a largely hydrophobic groove on PAS-B, overlapping with the surface engaged by the STAT6 transcription factor, suggesting that this mode of recruitment could be shared by diverse transcription factors including other nuclear receptors.

Original languageEnglish (US)
Article number167718
JournalJournal of Molecular Biology
Issue number16
StatePublished - Aug 30 2022


  • per-ARNT-sim domain
  • protein-protein interaction
  • solution NMR spectroscopy
  • steroid receptor coactivator
  • transcription regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Structural Biology


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