1XIU

Crystal structure of the agonist-bound ligand-binding domain of Biomphalaria glabrata RXR

Summary for 1XIU

• Entry DOI: 10.2210/pdb1xiu/pdb
• Related: 1FBY 1G1U 1LBD
• Descriptor: RXR-like protein, Nuclear receptor coactivator 1, (9cis)-retinoic acid, ... (4 entities in total)
• Functional Keywords: nuclear receptor, protein-ligand complex, retinoid receptor, transcription-transferase complex, transcription/transferase
• Biological source: Biomphalaria glabrata; More
• Cellular location: Nucleus : Q15788
• Total number of polymer chains: 4
• Total formula weight: 55955.07

Authors

De Groot, A.,De Rosny, E.,Juillan-Binard, C.,Ferrer, J.-L.,Laudet, V.,Pebay-Peroula, E.,Fontecilla-Camps, J.-C.,Borel, F. (deposition date: 2004-09-22, release date: 2005-09-13, Last modification date: 2023-08-23)

Primary citation

de Groot, A.,de Rosny, E.,Juillan-Binard, C.,Ferrer, J.-L.,Laudet, V.,Pierce, R.J.,Pebay-Peyroula, E.,Fontecilla-Camps, J.-C.,Borel, F.
Crystal Structure of a Novel Tetrameric Complex of Agonist-bound Ligand-binding Domain of Biomphalaria glabrata Retinoid X Receptor.
J.Mol.Biol., 354:841-853, 2005

PubMed Abstract: Nuclear receptors form an important class of transcription regulators in metazoans. To learn more about the evolution of these proteins, we have initiated structural studies on nuclear receptor ligand-binding domains from various animals. Here we present the crystal structure of the ligand-binding domain (LBD) of the retinoid X receptor (RXR) from the mollusc Biomphalaria glabrata. The structure reveals a novel tetrameric association in which each monomer is complexed to the human RXR ligand 9-cis retinoic acid and to a human co-activator-derived peptide. The ligand and the co-activator peptide are bound in essentially the same manner as observed in previously reported human RXR LBD structures, suggesting that the mechanisms of RXR-mediated transcription regulation are very similar in mollusc and human. The structure shows further that binding of ligand and co-activator peptide does not necessarily lead to the typical holo-conformation in which helix 12 (H12) folds back and packs against the LBD. Within a canonical dimer, only one monomer is in this closed agonist conformation. The other monomer is in an open conformation with H12 protruding from the LBD core, occupying the H12 interaction groove of another open monomer in an adjacent dimer in a domain swapping fashion, thus resulting in a tetrameric association. Additional tetramer interfaces are formed between H11 of the closed LBD and H6 of the open LBD. This novel holo-tetramer configuration may have a biological role in activating genes whose promoters are poorly recognised by dimers but much more efficiently by the corresponding tetramers.

PubMed: 16274693
DOI: 10.1016/j.jmb.2005.09.090

Experimental method

X-RAY DIFFRACTION (2.5 Å)