9.B.208 The Vitamin D3 Receptor (VDR) Family
The steroid hormone, vitamin D3, regulates gene transcription via at least two receptors and initiates putative rapid response systems at the plasma membrane. The vitamin D receptor (VDR) binds vitamin D3 and a second receptor, importin-4, imports the VDR-vitamin D3 complex into the nucleus via nuclear pores. Morrill et al. 2016 presented evidence that the Homo sapiens VDR homodimer contains two transmembrane (TM) helices ((327)E - D(342)), two TM 'half-helix' ((264)K N(276)), one or more large channels, and 16 cholesterol binding (CRAC/CARC) domains. The importin-4 monomer exhibits 3 pore- lining regions ((226)E - L(251); (768)V - G(783); (876)S - A(891)) and 16 CRAC/CARC domains. The MEMSAT algorithm indicated that VDR and importin-4 may not be restricted to cytoplasm and nucleus. The VDR homodimer TM helix-topology predicts insertion into the plasma membrane, with two 84 residue C-terminal regions being extracellular. Similarly, MEMSAT predicts importin-4 insertion into the plasma membrane with 226 residue extracellular N-terminal regions and 96 residue C-terminal extracellular loops; with the pore-lining regions contributing gated Ca2+ channels. The PoreWalker algorithm indicates that, of the 427 residues in each VDR monomer, 91 line the largest channel, including two vitamin D3 binding sites and residues from both the TM helix and 'half-helix'. Cholesterol-binding domains also extend into the channel within the ligand binding region. Programmed changes in bound cholesterol may regulate both membrane Ca2+ response systems and vitamin D3 uptake as well as receptor internalization by the endomembrane system culminating in uptake of the vitamin D3-VDR-importin-4 complex into the nucleus (Morrill et al. 2016).
The Vitamin D3 Receptor, VDR of 427 aas and 0 - 1 TMS. Possibly can insert into the plasma membrane and form a large channel (see family description) (Morrill et al. 2016). It is a dimer with two transmembrane half helices (264K - N276) and 16 cholesterol binding (CRAC/CARC) domains. May function with importin-4 (TC# 1.I.1.1.3) which may also be able to form a transmembrane channel (Morrill et al. 2016).
VDR of Homo sapiens
The bile acid Farnesoid receptor of 472 aas.
Farnesoid receptor of Homo sapiens