PDBsum entry 4cn5

Transcription/DNA

PDB id: 4cn5

Contents

Protein chains

81 a.a.

75 a.a.

DNA/RNA

Ligands

NO3

Metals

_CL ×5

_ZN ×4

__K ×4

Waters ×315

PDB id:

4cn5

Name:

Transcription/DNA

Title:

Crystal structure of the human retinoid x receptor DNA-binding domain bound to the human nr1d1 response element

Structure:

Retinoic acid receptor rxr-alpha. Chain: a, b. Fragment: DNA-binding domain, residues 126-212. Synonym: nuclear receptor subfamily 2 group b member 1, retinoid x receptor alpha. Engineered: yes. 5'-d( Tp Gp Gp Gp Gp Tp Cp Ap Gp Ap Gp Tp Tp Cp Ap Ap Tp)- 3'. Chain: c.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.00Å R-factor: 0.171 R-free: 0.227

Authors:

A.G.Mcewen,P.Poussin-Courmontagne,J.Osz,N.Rochel

Key ref:

J.Osz et al. (2015). Structural basis of natural promoter recognition by the retinoid X nuclear receptor. Sci Rep, 5, 8216. PubMed id: 25645674 DOI: 10.1038/srep08216

Date:

21-Jan-14 Release date: 18-Feb-15

Protein chain

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

Seq: 462 a.a.

Struc: 81 a.a.*

Protein chain

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

Seq: 462 a.a.

Struc: 75 a.a.

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

DNA/RNA chains

T-G-G-G-G-T-C-A-G-A-G-T-T-C-A-A-T 17 bases

A-T-T-G-A-A-C-T-C-T-G-A-C-C-C-C-A 17 bases

DOI no: 10.1038/srep08216

Sci Rep 5:8216 (2015)

PubMed id: 25645674

Structural basis of natural promoter recognition by the retinoid X nuclear receptor.

J.Osz, A.G.McEwen, P.Poussin-Courmontagne, E.Moutier, C.Birck, I.Davidson, D.Moras, N.Rochel.

ABSTRACT

Retinoid X receptors (RXRs) act as homodimers or heterodimerisation partners of class II nuclear receptors. RXR homo- and heterodimers bind direct repeats of the half-site (A/G)G(G/T)TCA separated by 1 nucleotide (DR1). We present a structural characterization of RXR-DNA binding domain (DBD) homodimers on several natural DR1s and an idealized symmetric DR1. Homodimers displayed asymmetric binding, with critical high-affinity interactions accounting for the 3' positioning of RXR in heterodimers on DR1s. Differing half-site and spacer DNA sequence induce changes in RXR-DBD homodimer conformation notably in the dimerization interface such that natural DR1s are bound with higher affinity than an idealized symmetric DR1. Subtle changes in the consensus DR1 DNA sequence therefore specify binding affinity through altered RXR-DBD-DNA contacts and changes in DBD conformation suggesting a general model whereby preferential half-site recognition determines polarity of heterodimer binding to response elements.