The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs.

Journal Article (Journal Article)

The vitamin D receptor (VDR) mediates the biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) through its capacity to recruit coregulatory proteins. This interaction is mediated via a coregulatory LxxLL motif. We screened a combinatorial (x)7LxxLL(x)7 phage library with purified VDR to identify peptides that displayed high affinity and selectivity for VDR. These peptides contained the consensus sequence Lx E/H x H/F P L/M/I LxxLL and exhibited significant sequence similarity to the active LxxLL box found in DRIP205. Nearly all LxxLL peptides interacted in a ligand-dependent manner directly with human VDR. However, a pattern of selectivity of the peptides for other members of the nuclear receptor family was also observed. Interestingly, the interaction between the VDR and many of the peptides was differentially sensitive to a broad assortment of VDR ligands. Finally, several of these peptides were shown to inhibit activation of a 1,25(OH)2D3-sensitive reporter gene. These studies suggest that the LxxLL motif can interact directly with the VDR and that this interaction is regulated by chemically diverse vitamin D ligands.

Full Text

Duke Authors

Cited Authors

  • Zella, LA; Chang, C-Y; McDonnell, DP; Pike, JW

Published Date

  • April 15, 2007

Published In

Volume / Issue

  • 460 / 2

Start / End Page

  • 206 - 212

PubMed ID

  • 17254542

Pubmed Central ID

  • 17254542

International Standard Serial Number (ISSN)

  • 0003-9861

Digital Object Identifier (DOI)

  • 10.1016/


  • eng

Conference Location

  • United States