Molecular Aspects of Vitamin D Hormone Action by muq18838


									      Molecular Aspects of Vitamin D Hormone Action

                                 Dr. Elaine Collins
                        San Jose State University, California

       The hormonally active form of vitamin D is 1,25-dihydroxy vitamin D3
[1,25(OH)2D3]. Biological actions of 1,25(OH)2D3 include maintaining calcium
homeostasis and affecting differentiation and proliferation of a variety of tissues
including skin, immune cells, and many cancer cells. Most of these actions are
mediated through the actions of its nuclear receptor (VDR). VDR is a member of
a superfamily of nuclear receptors which are ligand-dependent transcription
factors. Other members of the family include receptors for steroid hormones,
retinoids, thyroid hormone and several orphan receptors. Hormone binding to
VDR is an early step in the nuclear signaling pathway. Binding results in
conformational changes in the ligand binding domain (LBD) of the receptor. We
are investigating the molecular details of ligand binding and the relationship of
binding to conformational changes in LBD. Recently, the x-ray crystal structure
of the LBD was published. However, 50 amino acid residues were deleted from
the protein due to problems with the crystalization process. We are studying
binding characteristics of the native receptor and the deletion mutant to
determine the importance of the deleted residues in hormone binding. Our
experimental approach includes: 1) Construction of deletion mutants and point
mutations. 2) Binding assays to determine binding affinity of the mutant
receptors. These experiments should help define the role of 1,25(OH)2D3
binding in the vitamin D signal transduction pathway.

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