PDBsum entry 4umm

Nuclear receptor

PDB id: 4umm

Contents

Protein chains

78 a.a.

87 a.a.

241 a.a.

236 a.a.

DNA/RNA

Ligands

EPH

P1A

Waters ×8

PDB id:

4umm

Name:

Nuclear receptor

Title:

The cryo-em structure of the palindromic DNA-bound usp-ecr nuclear receptor reveals an asymmetric organization with allosteric domain positioning

Structure:

Ecr-usp. Chain: a. Engineered: yes. 5'-d( Cp Ap Ap Gp Gp Gp Tp Tp Cp Ap Ap Tp Gp Cp Ap Cp Tp Tp Gp Tp)-3'. Chain: c. Engineered: yes. 5'-d( Dgp Ap Cp Ap Ap Gp Tp Gp Cp Ap Tp Tp Gp Dap Ap Cp Cp Cp Tp T)-3'.

Source:

Heliothis virescens. Tobacco budworm. Organism_taxid: 7102. Organ: nucleous. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Authors:

M.Maletta,I.Orlov,D.Moras,I.M.L.Billas,B.P.Klaholz

Key ref:

M.Maletta et al. (2014). The palindromic DNA-bound USP/EcR nuclear receptor adopts an asymmetric organization with allosteric domain positioning. Nat Commun, 5, 4139. PubMed id: 24942373 DOI: 10.1038/ncomms5139

Date:

19-May-14 Release date: 25-Jun-14

Protein chain

No UniProt id for this chain

Struc: 78 a.a.

Protein chain

O18473  (ECR_HELVI) -  Ecdysone receptor from Heliothis virescens

Seq: 576 a.a.

Struc: 87 a.a.*

Protein chain

Q7SIF6  (Q7SIF6_HELVI) -  Gene regulation protein from Heliothis virescens

Seq: 264 a.a.

Struc: 241 a.a.

Protein chain

O18473  (ECR_HELVI) -  Ecdysone receptor from Heliothis virescens

Seq: 576 a.a.

Struc: 236 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DNA/RNA chains

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

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

Enzyme reactions

• Enzyme class: Chains E, F, G: E.C.?

DOI no: 10.1038/ncomms5139

Nat Commun 5:4139 (2014)

PubMed id: 24942373

The palindromic DNA-bound USP/EcR nuclear receptor adopts an asymmetric organization with allosteric domain positioning.

M.Maletta, I.Orlov, P.Roblin, Y.Beck, D.Moras, I.M.Billas, B.P.Klaholz.

ABSTRACT

Nuclear receptors (NRs) regulate gene expression through DNA- and ligand-binding and thus represent crucial therapeutic targets. The ultraspiracle protein/ecdysone receptor (USP/EcR) complex binds to half-sites with a one base pair spaced inverted repeat (IR1), a palindromic DNA response element (RE) reminiscent of IRs observed for vertebrate steroid hormone receptors. Here we present the cryo electron microscopy structure of the USP/EcR complex bound to an IR1 RE which provides the first description of a full IR-bound NR complex. The structure reveals that even though the DNA is almost symmetric, the complex adopts a highly asymmetric architecture in which the ligand-binding domains (LBDs) are positioned 5' off-centred. Additional interactions of the USP LBD with the 5'-flanking sequence trigger transcription activity as monitored by transfection assays. The comparison with DR-bound NR complexes suggests that DNA is the major allosteric driver in inversely positioning the LBDs, which serve as the main binding-site for transcriptional regulators.