PMID: 8948643Nov 15, 1996Paper

The high affinity ligand binding conformation of the nuclear 1,25-dihydroxyvitamin D3 receptor is functionally linked to the transactivation domain 2 (AF-2)

Nucleic Acids Research
S NayeriC Carlberg

Abstract

The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, is a transcription factor that mediates all genomic actions of the hormone. The activation of VDR by ligand induces a conformational change within its ligand binding domain (LBD). Due to the lack of a crystal structure analysis, biochemical methods have to be applied in order to investigate the details of this receptor-ligand interaction. The limited protease digestion assay can be used as a tool for the determination of a functional dissociation constant (K(df)) of VDR with any potential ligand. This method provided with the natural hormone VD two protease-resistant fragments of the VDR LBD and with the 20-epi conformation of VD, known as MC1288, even an additional fragment of intermediate size. These fragments were interpreted as different receptor conformations and their decreasing size was found to be associated with decreasing ligand binding affinity. A critical amino acid for VDR's high ligand binding conformation has been identified by C-terminal receptor truncations and point mutations as phenylalanine 422. This amino acid appears to directly contact the ligand and belongs to the ligand-inducible activation function-2 (AF-2) domain. Moreover, functional assays...Continue Reading

References

Nov 1, 1992·Endocrine Reviews·M R Walters
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Jan 26, 1996·Biochemical and Biophysical Research Communications·J P Kahlen, C Carlberg

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Citations

Jan 10, 2002·Journal of Molecular Biology·Sami VäisänenCarsten Carlberg
May 15, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Laura L IssaJohn A Eisman
Apr 24, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·L VerlindenR Bouillon
Nov 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lin-Yan WanJiang-Feng Wu
Mar 15, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Amanda M OusleyBahareh Azizi
Mar 20, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Sayaka MotoyoshiHiroaki Tokiwa
Feb 3, 2007·European Journal of Immunology·Evelyne van EttenChantal Mathieu
Mar 28, 2013·International Journal of Endocrinology·Monika Puzianowska-KuznickaJacek Polosak
Jun 26, 1999·The Journal of Biological Chemistry·A Racz, J Barsony
Jul 17, 2001·Journal of Cellular Biochemistry. Supplement·Y BuryC Carlberg
Jun 19, 2015·American Journal of Physiology. Renal Physiology·Tejinder SinghPravin C Singhal

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