4UMM

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

4UMM の概要

• エントリーDOI: 10.2210/pdb4umm/pdb
• EMDBエントリー: 2631
• 分子名称: ECR-USP, 5'-D(*CP*AP*AP*GP*GP*GP*TP*TP*CP*AP*AP*TP*GP*CP *AP*CP*TP*TP*GP*TP)-3', 5'-D(*DGP*AP*CP*AP*AP*GP*TP*GP*CP*AP*TP*TP*GP*DAP *AP*CP*CP*CP*TP*T)-3', ... (9 entities in total)
• 機能のキーワード: nuclear receptor, transcription, ecdysone, usp-ecr, dna response element, allostery, cryo electron microscopy
• 由来する生物種: HELIOTHIS VIRESCENS (TOBACCO BUDWORM); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 93129.98

構造登録者

Maletta, M.,Orlov, I.,Moras, D.,Billas, I.M.L.,Klaholz, B.P. (登録日: 2014-05-19, 公開日: 2014-06-25, 最終更新日: 2024-05-08)

主引用文献

Maletta, M.,Orlov, I.,Moras, D.,Billas, I.M.L.,Klaholz, B.P.
The Palindromic DNA-Bound Usp-Ecr Nuclear Receptor Adopts an Asymmetric Organization with Allosteric Domain Positioning.
Nat.Commun., 5:4139-, 2014

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 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.

PubMed: 24942373
DOI: 10.1038/NCOMMS5139

実験手法

ELECTRON MICROSCOPY (11.6 Å)