SRC2-3 binds to vitamin D receptor with high sensitivity and strong affinity

Bioorg Med Chem. 2017 Jan 15;25(2):568-574. doi: 10.1016/j.bmc.2016.11.020. Epub 2016 Nov 14.


Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and regulates the expression of target genes through ligand binding. To express the target gene, coactivator binding to the VDR/ligand complex is essential. Although there are many coactivators in living cells, precise interactions between coactivators and VDR have not been clarified. Here, we synthesized two coactivator peptides, DRIP205-2 and SRC2-3, evaluated their affinity for the ligand-binding domain (LBD) of VDR using 1α,25-dihydroxyvitamin D3, partial agonist 1, and antagonist 2 by surface plasmon resonance (SPR), and assessed their interaction modes with VDR-LBD using X-ray crystallographic analysis. This study showed that the SRC2-3 peptide is more sensitive to the ligands (agonist, partial agonist, and antagonist) and shows more intimate interactions with VDR-LBD than DRIP205-2 peptide.

Keywords: Charge clamp; Coactivator; Consensus motif; Nuclear receptor; SRC2-3; Surface plasmon resonance; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptides / pharmacology*
  • Receptors, Calcitriol / agonists
  • Receptors, Calcitriol / antagonists & inhibitors
  • Receptors, Calcitriol / chemistry
  • Receptors, Calcitriol / metabolism*
  • Structure-Activity Relationship
  • Surface Plasmon Resonance


  • Peptides
  • Receptors, Calcitriol