1xiu | pdb_00001xiu
Crystal structure of the agonist-bound ligand-binding domain of Biomphalaria glabrata RXR
Structural highlights
FunctionRXR_BIOGL Ligand-dependent transcription factor probably involved in the retinoic acid response pathway. Binds 9-cis-retinoic acid (9C-RA) and, to a lesser extent, docosahexaenoic acid (DHA), phytanic acid, methoprene acid and oleic acid. Binds to double-stranded DNA sequences containing direct repeats (DR) with the consensus sequence 5'-[AG]GGTCA-3' and 1, 2, 3, 4 or 5 nucleotides in between (DR1, DR2, DR3. DR4 and DR5, respectively). Binding to DR1 is strongest. Transactivates gene expression when 9C-RA or DHA is bound.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNuclear 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. Crystal structure of a novel tetrameric complex of agonist-bound ligand-binding domain of Biomphalaria glabrata retinoid X receptor.,de Groot A, de Rosny E, Juillan-Binard C, Ferrer JL, Laudet V, Pierce RJ, Pebay-Peyroula E, Fontecilla-Camps JC, Borel F J Mol Biol. 2005 Dec 9;354(4):841-53. Epub 2005 Oct 21. PMID:16274693[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
