Vitamin D Receptor Interacts with DnaK/Heat Shock Protein 70: Identification of DnaK Interaction Site on Vitamin D Receptor

• Published in: Archives of biochemistry and biophysics Vol. 363; no. 2; pp. 219 - 226
• Main Authors: Swamy, Narasimha, Mohr, Scott C., Xu, Wenrong, Ray, Rahul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.1999
• Subjects: Amino Acid Sequence; Bacterial Proteins - metabolism; Binding Sites - physiology; Binding, Competitive - genetics; Calcitriol - metabolism; DnaK; Escherichia coli Proteins; Glutathione Transferase - genetics; heat shock proteins; Hsp 70; HSP70 Heat-Shock Proteins - metabolism; Humans; Molecular Chaperones - metabolism; Molecular Sequence Data; Mutagenesis, Site-Directed; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Sequence Deletion - genetics; vitamin D receptor; vitamin D receptor ligand-binding domain; Hsp 70; vitamin D receptor; DnaK; vitamin D receptor ligand-binding domain; heat shock proteins
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1998.1079

Vitamin D receptor (VDR) regulates the expression of vitamin D-dependent genes upon binding to its cognate ligand, 1α,25-dihydroxyvitamin D3(1,25(OH)2D3). This process represents a complex interaction of ligand-bound VDR with nuclear proteins like retinoid X receptor, nuclear accessory factors, and regulatory elements of the target gene. Expression of full-length VDR inEscherichia colirevealed that VDR binds DnaK, a member of heat-shock protein (Hsp) family, with high affinity. By systematic N-terminal truncation of VDR, the interaction site of DnaK on VDR was localized within a 17-amino-acid segment (105–122) representing the “hinge region” between the DNA-binding and hormone-binding domains of VDR. The putative DnaK-binding site was further localized between residues 105 to 109 of VDR by using binding-energy-minimization studies. The interaction of DnaK with VDR did not influence the binding of 1,25(OH)2D3or nuclear accessory factor(s) to VDR. Furthermore, bovine brain Hsp 70, similar to DnaK, interacted with VDR–ligand-binding domain (105–427). These results suggest that DnaK/Hsp 70 may interact with VDR prior to the activation of the latter by 1,25(OH)2D3-binding.