The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand.

  title={The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand.},
  author={Natacha Rochel and Jean Marie Wurtz and André Mitschler and Bruno P. Klaholz and Dino Moras},
  journal={Molecular cell},
  volume={5 1},

Functional and structural characterization of nuclear vitamin D receptor and its ligand binding domain

In the present study recombinant human nuclear VDR and its ligand binding domain (LBD) were expressed in Spodoptera frugiperda insect cells and in E.coli cells and their biochemical and biophysical properties were purified.

Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands

The explanation of the superagonist effect is to be found in higher stability and longer half-life of the active complex, thereby excluding different conformations of the ligand binding domain.

Structural insights into the molecular mechanism of vitamin D receptor activation by lithocholic acid involving a new mode of ligand recognition.

Biological activity assays, structural analysis, and molecular dynamics simulations indicate that the recognition of two ligand molecules is crucial for VDR agonism by LCA, and the unique binding mode of LCA provides clues for the development of new chemical compounds that target alternative binding sites for therapeutic applications.

Vitamin D and Its Receptor from a Structural Perspective

An overview of the current knowledge of VDR structures is provided and the recent progress in understanding the complex mechanism of action of 1,25D3 from a structural perspective is explored.

Crystal structures of complexes of vitamin D receptor ligand-binding domain with lithocholic acid derivatives

The crystal structures of the ligand-binding domain of rat VDR (VDR-LBD) in ternary complexes with a synthetic partial peptide of the coactivator MED1 and four ligands, LCA, 3-keto LCA), LCA acetate, and LCA propionate are determined with the goal of elucidating their agonistic mechanism.

Structurally and functionally important amino acids of the agonistic conformation of the human vitamin D receptor.

The results suggest that structurally different agonists have distinct ligand-receptor interactions and that the amino acid residues H229, D232, E269, F279, and Y295 are critical for the agonistic conformation of the VDR.



Crystal structure of the RAR-γ ligand-binding domain bound to all-trans retinoic acid

The 2.0-Å crystal structure of the ligand-binding domain (LBD) of the human retinoic acid receptor (RAR)-γ bound to all-trans retinoic acid reveals the ligand-binding interactions and suggests an

Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α

The crystal structure of the human retinoid-X receptor RXR-α ligand-binding domain reveals a previously undiscovered fold of an antiparallel α-helical sandwich, packed as dimeric units. Two helices

A canonical structure for the ligand-binding domain of nuclear receptors

Mutant studies support a general mechanism for ligand-induced activation deduced from the comparison of the transcriptionally active RARγ holo- and inactive RXRα apo-LBD structures.

Conformational adaptation of agonists to the human nuclear receptor RARγ

The crystal structures of the hRARγ ligand-binding domain bound to either its other natural ligand 9-cis retinoic acid, or an RARγ-selective synthetic agonist (BMS961) are reported and the selectivity of different RAR ligands can be explained using B MS961 as a template.

Mechanisms and functions of vitamin D.

Experiments in mice have illustrated that the autoimmune diseases of multiple sclerosis and rheumatoid arthritis can be successfully treated with the vitamin D hormone and its analogs and may not have the side effects attributed to the cyclosporin immunosuppression therapies.

Atomic structure of progesterone complexed with its receptor

The 1.8 Å crystal structure of a progesterone-bound ligand-binding domain of the human progester one receptor is reported, which explains the receptor's selective affinity for progestins and establishes a common mode of recognition of 3-oxy steroids by the cognate receptors.

A structural role for hormone in the thyroid hormone receptor

A structural role for ligand is suggested, in establishing the active conformation of the receptor, that is likely to underlie hormonal regulation of gene expression for the nuclear receptors.

Selective Interaction of Vitamin D Receptor with Transcriptional Coactivators by a Vitamin D Analog

The present findings suggest that the structure of VDR is altered in a vitamin D analog-specific way, resulting in selective interactions of V DR with coactivators, which may specify the array of biological actions of a Vitamin D analog like OCT.

Three‐dimensional model of the ligand binding domain of the nuclear receptor for 1α,25‐dihydroxy‐vitamin D3

Mapping of four natural and one experimental point mutations of the VDR LBD, which result in ligand‐related receptor dysfunction, indicates the close proximity of these amino acids to the bound ligand.