1KV6

X-ray structure of the orphan nuclear receptor ERR3 ligand-binding domain in the constitutively active conformation

1KV6 の概要

• エントリーDOI: 10.2210/pdb1kv6/pdb
• 関連するPDBエントリー: 1ERE 1K4W 3ERD
• 分子名称: ESTROGEN-RELATED RECEPTOR GAMMA, steroid receptor coactivator 1 (3 entities in total)
• 機能のキーワード: transcriptionally active conformation in absence of ligand, structural proteomics in europe, spine, structural genomics, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (Probable): P62508
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55720.89

構造登録者

Greschik, H.,Wurtz, J.-M.,Sanglier, S.,Bourguet, W.,van Dorsselaer, A.,Moras, D.,Renaud, J.-P.,Structural Proteomics in Europe (SPINE) (登録日: 2002-01-25, 公開日: 2003-01-25, 最終更新日: 2023-08-16)

主引用文献

Greschik, H.,Wurtz, J.-M.,Sanglier, S.,Bourguet, W.,van Dorsselaer, A.,Moras, D.,Renaud, J.-P.
Structural and Functional Evidence for Ligand-Independent Transcriptional Activation by the Estrogen-Related Receptor 3
Mol.Cell, 9:303-313, 2002

PubMed Abstract: The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor 3 (ERR3) complexed with a steroid receptor coactivator-1 (SRC-1) peptide reveals a transcriptionally active conformation in absence of any ligand. The structure explains why estradiol does not bind ERRs with significant affinity. Docking of the previously reported ERR antagonists, diethylstilbestrol and 4-hydroxytamoxifen, requires structural rearrangements enlarging the ligand binding pocket that can only be accommodated with an antagonist LBD conformation. Mutant receptors in which the ligand binding cavity is filled up by bulkier side chains still interact with SRC-1 in vitro and are transcriptionally active in vivo, but are no longer efficiently inactivated by diethylstilbestrol or 4-hydroxytamoxifen. These results provide structural and functional evidence for ligand-independent transcriptional activation by ERR3.

PubMed: 11864604
DOI: 10.1016/S1097-2765(02)00444-6

実験手法

X-RAY DIFFRACTION (2.7 Å)