7A78
Crystal structure of RXR beta LBD in complexes with palmitic acid and GRIP-1 peptide
Summary for 7A78
| Entry DOI | 10.2210/pdb7a78/pdb |
| Descriptor | Retinoic acid receptor RXR-beta, Nuclear receptor coactivator 2, PALMITIC ACID, ... (6 entities in total) |
| Functional Keywords | rxrb, steroid hormone receptor, inhibitor, lipid binding, fatty acid, structural genomics consortium, sgc, dna binding protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 28787.77 |
| Authors | Chaikuad, A.,Merk, D.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2020-08-27, release date: 2020-10-21, Last modification date: 2024-01-31) |
| Primary citation | Chaikuad, A.,Pollinger, J.,Ruhl, M.,Ni, X.,Kilu, W.,Heering, J.,Merk, D. Comprehensive Set of Tertiary Complex Structures and Palmitic Acid Binding Provide Molecular Insights into Ligand Design for RXR Isoforms. Int J Mol Sci, 21:-, 2020 Cited by PubMed Abstract: The retinoid X receptor (RXR) is a ligand-sensing transcription factor acting mainly as a universal heterodimer partner for other nuclear receptors. Despite presenting as a potential therapeutic target for cancer and neurodegeneration, adverse effects typically observed for RXR agonists, likely due to the lack of isoform selectivity, limit chemotherapeutic application of currently available RXR ligands. The three human RXR isoforms exhibit different expression patterns; however, they share high sequence similarity, presenting a major obstacle toward the development of subtype-selective ligands. Here, we report the discovery of the saturated fatty acid, palmitic acid, as an RXR ligand and disclose a uniform set of crystal structures of all three RXR isoforms in an active conformation induced by palmitic acid. A structural comparison revealed subtle differences among the RXR subtypes. We also observed an ability of palmitic acid as well as myristic acid and stearic acid to induce recruitment of steroid receptor co-activator 1 to the RXR ligand-binding domain with low micromolar potencies. With the high, millimolar endogenous concentrations of these highly abundant lipids, our results suggest their potential involvement in RXR signaling. PubMed: 33187070DOI: 10.3390/ijms21228457 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.72 Å) |
Structure validation
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