spacer
spacer

PDBsum entry 1kb6
Go to PDB code: 
protein dna_rna metals Protein-protein interface(s) links
Transcription/DNA PDB id
1kb6

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
94 a.a. *
101 a.a. *
DNA/RNA
Metals
_ZN ×4
Waters ×34
* Residue conservation analysis
PDB id:
1kb6
Name: Transcription/DNA
Title: Crystal structure of vdr DNA-binding domain bound to rat osteocalcin (oc) response element
Structure: 5'-d( Cp Ap Cp Gp Gp Gp Tp Gp Ap Ap Tp Gp Ap Gp Gp Ap Cp A) -3'. Chain: c. Engineered: yes. Other_details: rat osteocalcin (oc) response element. 5'-d( Tp Gp Tp Cp Cp Tp Cp Ap Tp Tp Cp Ap Cp Cp Cp Gp Tp G) -3'. Chain: d. Engineered: yes.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: vdr. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
Resolution:
2.70Å     R-factor:   0.223     R-free:   0.275
Authors: P.L.Shaffer,D.T.Gewirth
Key ref:
P.L.Shaffer and D.T.Gewirth (2002). Structural basis of VDR-DNA interactions on direct repeat response elements. EMBO J, 21, 2242-2252. PubMed id: 11980721 DOI: 10.1093/emboj/21.9.2242
Date:
05-Nov-01     Release date:   03-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11473  (VDR_HUMAN) -  Vitamin D3 receptor from Homo sapiens
Seq:
Struc: 		427 a.a.
94 a.a.
Protein chain
Pfam   ArchSchema ?
P11473  (VDR_HUMAN) -  Vitamin D3 receptor from Homo sapiens
Seq:
Struc: 		427 a.a.
101 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

DNA/RNA chains
  C-A-C-G-G-G-T-G-A-A-T-G-A-G-G-A-C-A 18 bases
  T-G-T-C-C-T-C-A-T-T-C-A-C-C-C-G-T-G 18 bases

 

 
DOI no: 10.1093/emboj/21.9.2242 EMBO J 21:2242-2252 (2002)
PubMed id: 11980721  
 
 
Structural basis of VDR-DNA interactions on direct repeat response elements.
P.L.Shaffer, D.T.Gewirth.
 
  ABSTRACT  
 
The vitamin D receptor (VDR) forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by 3 bp of spacer DNA. We describe here the crystal structures at 2.7-2.8 A resolution of the VDR DNA-binding region (DBD) in complex with response elements from three different promoters: osteopontin (SPP), canonical DR3 and osteocalcin (OC). These structures reveal the chemical basis for the increased affinity of VDR for the SPP response element, and for the poor stability of the VDR-OC complex, relative to the canonical DR3 response element. The homodimeric protein-protein interface is stabilized by van der Waals interactions and is predominantly non-polar. An extensive alpha-helix at the C-terminal end of the VDR DBD resembles that found in the thyroid hormone receptor (TR), and suggests a mechanism by which VDR and TR discriminate among response elements. Selective structure-based mutations in the asymmetric homodimeric interface result in a VDR DBD protein that is defective in homodimerization but now forms heterodimers with the 9-cis retinoic acid receptor (RXR) DBD.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Protein and DNA constructs used in the structure determination. (A) The human VDR DBD. Sequence numbers are for full-length hVDR and those in parentheses refer to the common hormone receptor DBD numbering scheme. Residues in italics are disordered in all of the structures. (B) The 18 bp DNA duplexes used in co-crystallization, shown 5' arrow 3' in the top strand. Half-sites are shown in boxes and are numbered by base pair. The DR3 sequence contains a direct repeat of two consensus half-sites. SPP is the mouse osteopontin VDRE and OC is the rat osteocalcin VDRE. Bases that differ from the consensus sequence are shaded gray and the structurally significant changes are highlighted in black. Estimates of relative binding of VDR DBD homodimers to each sequence are also shown. 		Figure 3.
Figure 3 Experimental electron density and homodimeric assembly. (A) Unbiased experimental electron density from SAD phases. The map is contoured around the CTE of the upstream subunit of the VDR DBD−DR3 structure, which is shown as a C[ ]trace. (B) A portion of the 2F[o] = F[c] electron density map showing intersubunit dimerization contacts. (C) Stereo view of the dimerization interface in a van der Waals surface representation. (A) and (B) were made with Xtalview (McRee, 1999), and (C) was prepared with Ribbons.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 2242-2252) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21478865 N.Rochel, F.Ciesielski, J.Godet, E.Moman, M.Roessle, C.Peluso-Iltis, M.Moulin, M.Haertlein, P.Callow, Y.Mély, D.I.Svergun, and D.Moras (2011).
Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings.
  Nat Struct Mol Biol, 18, 564-570.  
19427329 A.di Masi, E.De Marinis, P.Ascenzi, and M.Marino (2009).
Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects.
  Mol Aspects Med, 30, 297-343.  
19553667 K.K.Hill, S.C.Roemer, D.N.Jones, M.E.Churchill, and D.P.Edwards (2009).
A progesterone receptor co-activator (JDP2) mediates activity through interaction with residues in the carboxyl-terminal extension of the DNA binding domain.
  J Biol Chem, 284, 24415-24424.  
  18612376 F.Claessens, S.Denayer, N.Van Tilborgh, S.Kerkhofs, C.Helsen, and A.Haelens (2008).
Diverse roles of androgen receptor (AR) domains in AR-mediated signaling.
  Nucl Recept Signal, 6, e008.  
18829458 P.Lu, G.B.Rha, M.Melikishvili, G.Wu, B.C.Adkins, M.G.Fried, and Y.I.Chi (2008).
Structural Basis of Natural Promoter Recognition by a Unique Nuclear Receptor, HNF4{alpha}: DIABETES GENE PRODUCT.
  J Biol Chem, 283, 33685-33697.
PDB code: 3cbb
18474528 S.C.Roemer, J.Adelman, M.E.Churchill, and D.P.Edwards (2008).
Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding.
  Nucleic Acids Res, 36, 3655-3666.  
17307735 K.Saavalainen, M.I.Tammi, T.Bowen, M.L.Schmitz, and C.Carlberg (2007).
Integration of the activation of the human hyaluronan synthase 2 gene promoter by common cofactors of the transcription factors retinoic acid receptor and nuclear factor kappaB.
  J Biol Chem, 282, 11530-11539.  
17426125 M.Jakób, R.Kołodziejczyk, M.Orłowski, S.Krzywda, A.Kowalska, J.Dutko-Gwóźdź, T.Gwóźdź, M.Kochman, M.Jaskólski, and A.Ozyhar (2007).
Novel DNA-binding element within the C-terminal extension of the nuclear receptor DNA-binding domain.
  Nucleic Acids Res, 35, 2705-2718.
PDB code: 2han
17014620 M.Wjst (2006).
The vitamin D slant on allergy.
  Pediatr Allergy Immunol, 17, 477-483.  
16931575 S.C.Roemer, D.C.Donham, L.Sherman, V.H.Pon, D.P.Edwards, and M.E.Churchill (2006).
Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.
  Mol Endocrinol, 20, 3042-3052.
PDB code: 2c7a
16085755 J.E.Donald, and E.I.Shakhnovich (2005).
Predicting specificity-determining residues in two large eukaryotic transcription factor families.
  Nucleic Acids Res, 33, 4455-4465.  
15722343 K.Saavalainen, S.Pasonen-Seppänen, T.W.Dunlop, R.Tammi, M.I.Tammi, and C.Carlberg (2005).
The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal growth factor responding gene.
  J Biol Chem, 280, 14636-14644.  
16204233 R.Yasmin, R.M.Williams, M.Xu, and N.Noy (2005).
Nuclear import of the retinoid X receptor, the vitamin D receptor, and their mutual heterodimer.
  J Biol Chem, 280, 40152-40160.  
15037741 P.L.Shaffer, A.Jivan, D.E.Dollins, F.Claessens, and D.T.Gewirth (2004).
Structural basis of androgen receptor binding to selective androgen response elements.
  Proc Natl Acad Sci U S A, 101, 4758-4763.
PDB code: 1r4i
14739282 V.S.Melvin, C.Harrell, J.S.Adelman, W.L.Kraus, M.Churchill, and D.P.Edwards (2004).
The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB.
  J Biol Chem, 279, 14763-14771.  
14592980 S.Devarakonda, J.M.Harp, Y.Kim, A.Ozyhar, and F.Rastinejad (2003).
Structure of the heterodimeric ecdysone receptor DNA-binding complex.
  EMBO J, 22, 5827-5840.
PDB codes: 1r0n 1r0o
12107189 G.Verrijdt, K.Schauwaers, A.Haelens, W.Rombauts, and F.Claessens (2002).
Functional interplay between two response elements with distinct binding characteristics dictates androgen specificity of the mouse sex-limited protein enhancer.
  J Biol Chem, 277, 35191-35201.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

spacer
spacer