4UMM: The Cryo-em Structure Of The Palindromic Dna-bound Usp-ecr Nuclear Receptor Reveals An Asymmetric Organization With Allosteric Domain Positioning

Citation:
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 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.
PDB ID: 4UMMDownload
MMDB ID: 121067
PDB Deposition Date: 2014/5/19
Updated in MMDB: 2014/07
Experimental Method:
electron microscopy
Resolution: 11.6  Å
Source Organism:
Spodoptera litura
Similar Structures:
Biological Unit for 4UMM: hexameric; determined by software (PISA)
Molecular Components in 4UMM
Label Count Molecule
Proteins (4 molecules)
1
Ecr-usp
Molecule annotation
1
Ecdysone Receptor
Molecule annotation
1
Gene Regulation Protein
Molecule annotation
1
Ecdysone Receptor
Molecule annotation
Nucleotides(2 molecules)
1
5'-d(*cp*ap*ap*gp*gp*gp*tp*tp*cp*ap*ap*tp*gp*cp *ap*cp*tp*tp*gp*tp)-3'
Molecule annotation
1
5'-d(*dgp*ap*cp*ap*ap*gp*tp*gp*cp*ap*tp*tp*gp*dap *ap*cp*cp*cp*tp*t)-3'
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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