PDBsum entry: 1dsz

Transcription/DNA

PDB id: 1dsz

Contents

Protein chains

75 a.a. *

84 a.a. *

DNA/RNA

Metals

_ZN ×4

Waters ×338

* Residue conservation analysis

PDB id:

1dsz

Name:

Transcription/DNA

Title:

Structure of the rxr/rar DNA-binding domain heterodimer in complex with the retinoic acid response element dr1

Structure:

DNA (5'- d( Cp Ap Gp Gp Tp Cp Ap Ap Ap Gp Gp Tp Cp Ap G)-3'). Chain: c. Engineered: yes. DNA (5'- d( Cp Tp Gp Ap Cp Cp Tp Tp Tp Gp Ap Cp Cp Tp G)-3'). Chain: d. Engineered: yes. Retinoic acid receptor alpha.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

1.70Å R-factor: 0.198 R-free: 0.267

Authors:

F.Rastinejad,T.Wagner,Q.Zhao,S.Khorasanizadeh

Key ref:

F.Rastinejad et al. (2000). Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1. EMBO J, 19, 1045-1054. PubMed id: 10698945 DOI: 10.1093/emboj/19.5.1045

Date:

10-Jan-00 Release date: 10-Jul-00

Protein chain

P10276  (RARA_HUMAN) -  Retinoic acid receptor alpha

Seq: 462 a.a.

Struc: 75 a.a.

Protein chain

P19793  (RXRA_HUMAN) -  Retinoic acid receptor RXR-alpha

Seq: 462 a.a.

Struc: 84 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: DNA binding (7 terms)

DOI no: 10.1093/emboj/19.5.1045

EMBO J 19:1045-1054 (2000)

PubMed id: 10698945

Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.

F.Rastinejad, T.Wagner, Q.Zhao, S.Khorasanizadeh.

ABSTRACT

The 9-cis retinoic acid receptor (retinoid X receptor, RXR) forms heterodimers with the all-trans retinoic acid receptor (RAR) and other nuclear receptors on DNA regulatory sites composed of tandem binding elements. We describe the 1.70 A resolution structure of the ternary complex of RXR and RAR DNA-binding regions in complex with the retinoic acid response element DR1. The receptors recognize identical half-sites through extensive base-specific contacts; however, RXR binds exclusively to the 3' site to form an asymmetric complex with the reverse polarity of other RXR heterodimers. The subunits associate in a strictly DNA-dependent manner using the T-box of RXR and the Zn-II region of RAR, both of which are reshaped in forming the complex. The protein-DNA contacts, the dimerization interface and the DNA curvature in the RXR-RAR complex are distinct from those of the RXR homodimer, which also binds DR1. Together, these structures illustrate how the nuclear receptor superfamily exploits conformational flexibility and locally induced structures to generate combinatorial transcription factors.

Selected figure(s)

Figure 3.
Figure 3 Stereo diagrams showing the contacts between the protein subunits. (A) The RXR–RAR interface involves the DNA minor groove and well ordered water molecules (red spheres). Dotted lines indicate hydrogen-bonding between atoms. The yellow spheres indicate the positions of the Zn-II atoms. Arg75 and Asn51 form complementary van der Waals interactions. (B) The corresponding region of the RXR–DBD homodimer interface on DR1 (Zhao et al., 2000). These and the following molecular display graphics were made using the program Ribbons (Carson and Bugg, 1986).

Figure 5.
Figure 5 DNA sequence recognition by RXR and RAR. (A) A view along the DNA-recognition helix ( 1) of RAR showing residues Tyr13, Arg26, Lys22, Glu19 and Arg27 and their direct and water-mediated base contacts. Hydrogen-bonds and water molecules are shown as dotted blue lines and red spheres, respectively. The DNA sequence is numbered as in Figure 1B. (B) The corresponding view of the RXR interface. (C) Summary of the protein–DNA contacts of RAR. Bridging water molecules are shown as black circles. The base pairs in blue form the consensus AGGTCA recognition element. The gray circles indicate the DNA phosphates. (D) Summary of RXR–DNA interactions. The base pairs in orange form the consensus element.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 1045-1054) copyright 2000.

Figures were selected by the author.