α-Helix-peptides comprising the human nuclear receptor ERRγ competitively provoke inhibition of functional homomeric dimerization

Xiaohui Liu, Hirokazu Nishimura, Akina Fujiyama, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Estrogen-related receptor γ (ERRγ) is a constitutively active nuclear receptor functioning as a transcription factor. ERRγ binds to a single half site designated as ERRE that has only a single DNA-binding motif. However, with regard to the subunit structure, it remains a matter of controversy whether ERRγ binds as a monomer or dimer. Because the ligand-binding domain (LBD) of ERRγ was in a homodimer form in its X-ray crystal structure, the peptide fragments present in the dimer interfaces would perturb or destabilize the dimer structure by inhibiting the mutual interaction among ERRγ molecules. Thus, to demonstrate the essential homodimer structure of ERRγ, we utilized the peptides corresponding to the α-helix peptides 7 (H7), H9, and H10/11 in order to test such inhibitor activity. These selections were done based on a structural analysis of the X-ray crystal structures of ERRγ-LBD, which forms a head-to-head dimer structure. Peptides were evaluated by means of a luciferase reporter gene assay, in which ERRγ exhibited a high constitutive activity with no ligand. When the peptide was expressed in the HeLa cells together with ERRγ, these peptides clearly showed a concentration-dependent activity inhibition, indicating that ERRγ is indeed homodimerized as required for DNA transcription activity. The present results strongly suggest that human nuclear receptor ERRγ functions as a genuine homomeric dimer with symmetrical dimeric interface regions.

Original languageEnglish
Pages (from-to)547-554
Number of pages8
JournalBiopolymers
DOIs
Publication statusPublished - Nov 4 2016

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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