Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA.
Level 5 - mechanism / opinion, no new human data
In vitro structural biology study (bench research with no clinical human data)
PubMed 22179700 · doi:10.1038/emboj.2011.445
What was done
The authors used cryo-electron microscopy (cryo-EM) to determine the structure of the 100-kDa heterodimeric complex of full-length liganded human retinoid X receptor (RXR) and vitamin D receptor (VDR) bound to a consensus direct repeat (DR3) DNA response element, fitting crystal structures of the individual ligand- and DNA-binding domains into the EM map.
What was found
No numerical values are reported in the abstract. Qualitatively, the 100-kDa complex adopts an asymmetric topology where the ligand-binding domains are positioned perpendicular to the DNA at the 5'-end of the response element, the VDR N-terminal A/B domain lies close to the DNA, and the visible hinges maintain an open conformation capable of binding co-regulators, with the helical hinge of VDR acting as a conserved linker.
Why it matters
The findings elucidate the structural basis for RXR acting as an adaptive partner in nuclear receptor heterodimers and clarify how the intact RXR/VDR complex coordinates DNA binding and co-regulator recruitment.
Limits
This is an in vitro structural investigation that does not measure in vivo functional endpoints, transcriptomic outputs, or human clinical outcomes. The abstract reports no quantitative resolution values or binding constants.
Cited by
- supports The vitamin D receptor heterodimerizes with the retinoid X receptor before binding to DNA.