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Title | The palindromic DNA-bound USP/EcR nuclear receptor adopts an asymmetric organization with allosteric domain positioning. |
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Journal, issue, pages | Nat Commun, Vol. 5, Page 4139, Year 2014 |
Publish date | Jun 19, 2014 |
Authors | Massimiliano Maletta / Igor Orlov / Pierre Roblin / Yannick Beck / Dino Moras / Isabelle M L Billas / Bruno P Klaholz / |
PubMed Abstract | Nuclear receptors (NRs) regulate gene expression through DNA- and ligand-binding and thus represent crucial therapeutic targets. The ultraspiracle protein/ecdysone receptor (USP/EcR) complex binds to ...Nuclear receptors (NRs) regulate gene expression through DNA- and ligand-binding and thus represent crucial therapeutic targets. The ultraspiracle protein/ecdysone receptor (USP/EcR) complex binds to half-sites with a one base pair spaced inverted repeat (IR1), a palindromic DNA response element (RE) reminiscent of IRs observed for vertebrate steroid hormone receptors. Here we present the cryo electron microscopy structure of the USP/EcR complex bound to an IR1 RE which provides the first description of a full IR-bound NR complex. The structure reveals that even though the DNA is almost symmetric, the complex adopts a highly asymmetric architecture in which the ligand-binding domains (LBDs) are positioned 5' off-centred. Additional interactions of the USP LBD with the 5'-flanking sequence trigger transcription activity as monitored by transfection assays. The comparison with DR-bound NR complexes suggests that DNA is the major allosteric driver in inversely positioning the LBDs, which serve as the main binding-site for transcriptional regulators. |
External links | Nat Commun / PubMed:24942373 |
Methods | EM (single particle) |
Resolution | 11.6 Å |
Structure data | EMDB-2631: The Cryo-EM structure of the palindromic DNA-bound USP/EcR nuclear receptor reveals an asymmetric organization with allosteric domain positioning |
Chemicals | ChemComp-EPH: ChemComp-P1A: ChemComp-HOH: |
Source |
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Keywords | NUCLEAR RECEPTOR / TRANSCRIPTION / ECDYSONE / USP-ECR / DNA RESPONSE ELEMENT / ALLOSTERY / CRYO ELECTRON MICROSCOPY |