3KMR
Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment
Summary for 3KMR
| Entry DOI | 10.2210/pdb3kmr/pdb |
| Descriptor | Retinoic acid receptor alpha, Nuclear receptor coactivator 1, 4-{[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl]amino}benzoic acid, ... (4 entities in total) |
| Functional Keywords | nuclear receptor transcription factor ligand binding domain, dna-binding, metal-binding, nucleus, phosphoprotein, proto-oncogene, receptor, transcription, transcription regulation, zinc-finger, activator, acyltransferase, isopeptide bond, transferase |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: P10276 Nucleus (By similarity): Q15788 |
| Total number of polymer chains | 2 |
| Total formula weight | 31910.91 |
| Authors | Bourguet, W.,Teyssier, C. (deposition date: 2009-11-11, release date: 2010-06-02, Last modification date: 2023-09-06) |
| Primary citation | le Maire, A.,Teyssier, C.,Erb, C.,Grimaldi, M.,Alvarez, S.,de Lera, A.R.,Balaguer, P.,Gronemeyer, H.,Royer, C.A.,Germain, P.,Bourguet, W. A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor. Nat.Struct.Mol.Biol., 17:801-807, 2010 Cited by PubMed Abstract: In the absence of ligand, some nuclear receptors, including retinoic acid receptor (RAR), act as transcriptional repressors by recruiting corepressor complexes to target genes. This constitutive repression is crucial in metazoan reproduction, development and homeostasis. However, its specific molecular determinants had remained obscure. Using structural, biochemical and cell-based assays, we show that the basal repressive activity of RAR is conferred by an extended beta-strand that forms an antiparallel beta-sheet with specific corepressor residues. Agonist binding induces a beta-strand-to-alpha-helix transition that allows for helix H11 formation, which in turn provokes corepressor release, repositioning of helix H12 and coactivator recruitment. Several lines of evidence suggest that this structural switch could be implicated in the intrinsic repressor function of other nuclear receptors. Finally, we report on the molecular mechanism by which inverse agonists strengthen corepressor interaction and enhance gene silencing by RAR. PubMed: 20543827DOI: 10.1038/nsmb.1855 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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