PDBsum entry 4zsh

Transcription

PDB id: 4zsh

Contents

Protein chains

213 a.a.

11 a.a.

Ligands

4XW

Waters ×181

PDB id:

4zsh

Name:

Transcription

Title:

Rxr lbd in complex with 9-cis-13,14-dihydroretinoic acid

Structure:

Retinoic acid receptor rxr-alpha. Chain: a. Fragment: residues 223 - 462. Synonym: nuclear receptor subfamily 2 group b member 1,retinoid x receptor alpha. Engineered: yes. Other_details: ligand binding domain. Ncoa2 peptide. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rxra, nr2b1. Expressed in: escherichia coli 'bl21-gold(de3)plyss ag'. Expression_system_taxid: 866768. Expression_system_variant: plyss ag. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.80Å R-factor: 0.209 R-free: 0.218

Authors:

N.Rochel,W.Krezel,R.Ruhl

Key ref:

R.Rühl et al. (2015). 9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice. Plos Genet, 11, e1005213. PubMed id: 26030625 DOI: 10.1371/journal.pgen.1005213

Date:

13-May-15 Release date: 30-Mar-16

Protein chain

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

Seq: 462 a.a.

Struc: 213 a.a.

Protein chain

Q15596  (NCOA2_HUMAN) -  Nuclear receptor coactivator 2 from Homo sapiens

Seq: 1464 a.a.

Struc: 11 a.a.

DOI no: 10.1371/journal.pgen.1005213

Plos Genet 11:e1005213 (2015)

PubMed id: 26030625

9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice.

R.Rühl, A.Krzyżosiak, A.Niewiadomska-Cimicka, N.Rochel, L.Szeles, B.Vaz, M.Wietrzych-Schindler, S.Álvarez, M.Szklenar, L.Nagy, A.R.de Lera, W.Krężel.

ABSTRACT

The retinoid X receptors (RXRs) are ligand-activated transcription factors which heterodimerize with a number of nuclear hormone receptors, thereby controlling a variety of (patho)-physiological processes. Although synthetic RXR ligands are developed for the treatment of various diseases, endogenous ligand(s) for these receptors have not been conclusively identified. We show here that mice lacking cellular retinol binding protein (Rbp1-/-) display memory deficits reflecting compromised RXR signaling. Using HPLC-MS and chemical synthesis we identified in Rbp1-/- mice reduced levels of 9-cis-13,14-dihydroretinoic acid (9CDHRA), which acts as an RXR ligand since it binds and transactivates RXR in various assays. 9CDHRA rescues the Rbp1-/- phenotype similarly to a synthetic RXR ligand and displays similar transcriptional activity in cultured human dendritic cells. High endogenous levels of 9CDHRA in mice indicate physiological relevance of these data and that 9CDHRA acts as an endogenous RXR ligand.