4umm | pdb_00004umm

The Cryo-EM structure of the palindromic DNA-bound USP-EcR nuclear receptor reveals an asymmetric organization with allosteric domain positioning

Loading... Status: waiting for Mol* initialization Structural highlights 4umm is a 6 chain structure with sequence from Heliothis virescens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 11.6Å Ligands: EPH, P1A Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ECR_HELVI Receptor for ecdysone. Binds to ecdysone response elements (ECRES) (By similarity). Publication Abstract from PubMed 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. The palindromic DNA-bound USP/EcR nuclear receptor adopts an asymmetric organization with allosteric domain positioning.,Maletta M, Orlov I, Roblin P, Beck Y, Moras D, Billas IM, Klaholz BP Nat Commun. 2014 Jun 19;5:4139. doi: 10.1038/ncomms5139. PMID:24942373 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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