PDBsum entry 1a6y

Transcription/DNA

PDB id: 1a6y

Contents

Protein chains

78 a.a. *

84 a.a. *

DNA/RNA

Metals

_ZN ×4

Waters ×234

* Residue conservation analysis

PDB id:

1a6y

Name:

Transcription/DNA

Title:

Reverba orphan nuclear receptor/DNA complex

Structure:

DNA (5'-d( Cp Ap Ap Cp Tp Ap Gp Gp Tp Cp Ap Cp (5It) p Ap Gp Gp Tp Cp Ap G)-3'). Chain: c. Engineered: yes. DNA (5'- d( Cp Tp Gp Ap Cp Cp Tp Ap Gp Tp Gp Ap Cp Cp Tp Ap Gp Tp Tp G)-3'). Chain: d. Engineered: yes. Orphan nuclear receptor nr1d1.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.30Å R-factor: 0.192 R-free: 0.288

Authors:

Q.Zhao,S.Khorasanizadeh,F.Rastinejad

Key ref:

Q.Zhao et al. (1998). Structural elements of an orphan nuclear receptor-DNA complex. Mol Cell, 1, 849-861. PubMed id: 9660968 DOI: 10.1016/S1097-2765(00)80084-2

Date:

04-Mar-98 Release date: 21-Oct-98

Protein chain

P20393  (NR1D1_HUMAN) -  Nuclear receptor subfamily 1 group D member 1 from Homo sapiens

Seq: 614 a.a.

Struc: 78 a.a.*

Protein chain

P20393  (NR1D1_HUMAN) -  Nuclear receptor subfamily 1 group D member 1 from Homo sapiens

Seq: 614 a.a.

Struc: 84 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DNA/RNA chains

C-A-A-C-T-A-G-G-T-C-A-C-5IU-A-G-G-T-C-A-G 20 bases

C-T-G-A-C-C-T-A-G-T-G-A-C-C-T-A-G-T-T-G 20 bases

DOI no: 10.1016/S1097-2765(00)80084-2

Mol Cell 1:849-861 (1998)

PubMed id: 9660968

Structural elements of an orphan nuclear receptor-DNA complex.

Q.Zhao, S.Khorasanizadeh, Y.Miyoshi, M.A.Lazar, F.Rastinejad.

ABSTRACT

The nuclear hormone receptors form the largest known family of transcription factors. The current notion of receptor DNA discrimination, based solely on one major type of hexameric half-site and a highly conserved 66-residue core DNA-binding domain (DBD), does not adequately describe how more than 150 nonsteroid receptors differentiate among response elements. Here, we describe the 2.3 A crystal structure of the DNA-binding region of the orphan receptor RevErb arranged as a tandem homodimer on its optimal response element. The structure reveals the presence of a second major protein-DNA interface adjacent to the classical one involving the half-sites. A sequence comparison of orphan receptors suggests that unique minor-groove interactions involving the receptor hinge regions impart the necessary DNA and dimerization specificity.

Selected figure(s)

Figure 1.
Figure 1. The Protein and DNA Constructs Used in Crystallization and Their Contacts(a and b) The upstream (a) and downstream (b) positioned DNA-binding regions of human RevErbα are numbered starting with the first conserved cysteine. The authentic numbers appear in the parentheses. Dashed lines indicate amino- and carboxy-terminal residues not found in the electron density maps. Closed and open arrows indicate direct and water-mediated hydrogen bonds to the DNA bases, respectively. Closed and open boxes indicate direct and water-mediated hydrogen bonds to the DNA phosphates. Colored circles indicate Van der Waals contacts with the DNA, and closed black circles indicate residues that mediate subunit dimerization. A symbol indicates one or more such contacts.(c) The 20 base pair DNA is numbered from the 5′ end, with arrows indicating the half-site repeats and boxes indicating the spacer and 5′ flanking sequence. Shown are the upstream (green) and downstream (red) contacts from the RevErb subunits.

Figure 2.
Figure 2. Overall Architecture of the Complex(a) The overall architecture of the complex. The green polypeptide and the red polypeptides are the upstream and downstream subunits, respectively. Zincs are shown as gray spheres. The conserved AGGTCA half-sites are shown in purple, and the 5′ flanking base pairs and spacer are shown in yellow.(b) Surface representation of the protein–DNA complex. The view is nearly identical to that shown in (a). The location of the Grip box in the minor groove is indicated.(c) Stereo diagram of the overall complex, showing the side chains (in yellow) mediating direct protein–DNA contacts and those coordinating the zinc ions (in pink). The green polypeptide is the upstream subunit. The yellow spheres are zincs, and their coordinating cysteines are in pink. The numbers along the DNA indicate the sequence as shown in Figure 1c.Half-Site Contacts(d and e) Schematic summary of upstream (d) and downstream (e) contacts between the core DBD and the half-sites. Red arrows indicate hydrogen bonding to the DNA phosphates; black arrows indicate other hydrogen bonds. The arrowhead indicates the probable hydrogen-bond acceptor. The contacts involve the side chains, unless otherwise stated. Amino acids in black make at least one direct hydrogen bond to the DNA bases. Residues circled in green make different DNA interactions in the two subunits. The blue circles are water molecules that mediate protein–DNA contacts. The yellow base pairs are different in steroid-receptor response elements. The DNA shown is underwound for clarity.

The above figures are reprinted by permission from Cell Press: Mol Cell (1998, 1, 849-861) copyright 1998.

Figures were selected by an automated process.