PDBsum entry 1by4

Gene regulation/DNA

PDB id: 1by4

Contents

Protein chains

79 a.a. *

82 a.a. *

DNA/RNA

Metals

_ZN ×8

Waters ×230

* Residue conservation analysis

PDB id:

1by4

Name:

Gene regulation/DNA

Title:

Structure and mechanism of the homodimeric assembly of the rxr on DNA

Structure:

DNA (5'-d( C Tp Ap Gp Gp Tp Cp Ap Ap Ap Gp Gp Tp Cp Ap G)- 3'). Chain: e, g. Engineered: yes. DNA (5'-d( Cp Tp Gp Ap Cp Cp Tp Tp Tp Gp Ap Cp Cp Tp A)- 3'). Chain: f, h. Engineered: yes. Protein (retinoic acid receptor rxr-alpha).

Source:

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

Biol. unit:

Tetramer (from PQS)

Resolution:

2.10Å R-factor: 0.234 R-free: 0.284

Authors:

Q.Zhao,S.A.Chasse,S.Devarakonda,M.L.Sierk,B.Ahvazi,P.B.Sigler, F.Rastinejad

Key ref:

Q.Zhao et al. (2000). Structural basis of RXR-DNA interactions. J Mol Biol, 296, 509-520. PubMed id: 10669605 DOI: 10.1006/jmbi.1999.3457

Date:

22-Oct-98 Release date: 12-Jan-00

Protein chains

P19793  (RXRA_HUMAN) -  Retinoic acid receptor RXR-alpha from Homo sapiens

Seq: 462 a.a.

Struc: 79 a.a.

Protein chains

P19793  (RXRA_HUMAN) -  Retinoic acid receptor RXR-alpha from Homo sapiens

Seq: 462 a.a.

Struc: 82 a.a.*

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

DNA/RNA chains

T-A-G-G-T-C-A-A-A-G-G-T-C-A-G 15 bases

C-T-G-A-C-C-T-T-T-G-A-C-C-T-A 15 bases

C-T-A-G-G-T-C-A-A-A-G-G-T-C-A-G 16 bases

C-T-G-A-C-C-T-T-T-G-A-C-C-T-A 15 bases

DOI no: 10.1006/jmbi.1999.3457

J Mol Biol 296:509-520 (2000)

PubMed id: 10669605

Structural basis of RXR-DNA interactions.

Q.Zhao, S.A.Chasse, S.Devarakonda, M.L.Sierk, B.Ahvazi, F.Rastinejad.

ABSTRACT

The 9-cis retinoic acid receptor, RXR, binds DNA effectively as a homodimer or as a heterodimer with other nuclear receptors. The DNA-binding sites for these RXR complexes are direct repeats of a consensus sequence separated by one to five base-pairs of intervening space. Here, we report the 2.1 A crystal structure of the RXR-DNA-binding domain as a homodimer in complex with its idealized direct repeat DNA target. The structure shows how a gene-regulatory site can induce conformational changes in a transcription factor that promote homo-cooperative assembly. Specifically, an alpha-helix in the T-box is disrupted to allow efficient DNA-binding and subunit dimerization. RXR displays a relaxed mode of sequence recognition, interacting with only three base-pairs in each hexameric half-site. The structure illustrates how site selection is achieved in this large eukaryotic transcription factor family through discrete protein-protein interactions and the use of tandem DNA binding sites with characteristic spacings.

Selected figure(s)

Figure 3.
Figure 3. Protein-DNA and protein-protein interactions at the dimer interfaces. (a) Close-up view of the protein-protein contacts in the DR1 complex formed by subunits 1 and 2, and equivalently by subunits 3 and 4. The pink bars indicate the position of the spacer base-pair(s). Side-chains shown are only those making DNA or dimerization contacts. Hydrogen bonding between the side-chains of residues 49, 52 and 74, which form the dimerization contacts, are shown by broken lines. Figures were generated with Ribbons [Carson and Bugg 1986]. (b) The corresponding view at the "DR2" site. (c) Surface complementarity in the protein-protein interface on DR1, with subunit 1 shown in red and subunit 2 shown in white. The location of the DNA is shown for reference, with the 5' end pointing up [Nicholls et al 1991]. (d) The corresponding view at the "DR2" interface, with subunit 2 (white) and subunit 3 (blue). (e) Fluorescence anisotropy measurements showing the binding of RXR-DBD to DR1 (black circles) and DR2 (red squares). The maximal values for fluorescence aniostropy differ for the DR1 and DR2 plots, as expected from the different binding geometries and solution reorientation properties of these complexes.

Figure 6.
Figure 6. Similarities among the structurally characterized DBD-DNA complexes. Comparison of the (a) RXR DBD-DNA complex on DR1 with those of the (b) RXR-TR DBD on DR4 [Rastinejad et al 1995], (c) the RevErb homodimer on DR2 [Zhao et al 1998] and (d) the glucocorticoid DBD complex on a symmetric repeat Pal3 [Luisi et al 1991]. In each case, the DNA is shown with the 5' end at the top, and the spacer base-pairs are colored pink.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 296, 509-520) copyright 2000.

Figures were selected by an automated process.