1G5Y

THE 2.0 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE RXRALPHA LIGAND BINDING DOMAIN TETRAMER IN THE PRESENCE OF A NON-ACTIVATING RETINOIC ACID ISOMER.

1G5Y の概要

• エントリーDOI: 10.2210/pdb1g5y/pdb
• 関連するPDBエントリー: 1FM6 1FM9 1G1U 1LBD
• 分子名称: RETINOIC ACID RECEPTOR RXR-ALPHA, RETINOIC ACID (3 entities in total)
• 機能のキーワード: rxralpha ligand binding domain, inactive tetramer with 2 monomers bound with an inactivating isomer of retinoic acid, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : P19793
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 107272.30

構造登録者

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Wisely, G.B.,Milburn, M.V.,Xu, H.E. (登録日: 2000-11-02, 公開日: 2001-05-02, 最終更新日: 2024-10-16)

主引用文献

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Wisely, G.B.,Milburn, M.V.,Xu, H.E.
Structural basis for autorepression of retinoid X receptor by tetramer formation and the AF-2 helix.
Genes Dev., 14:2229-2241, 2000

PubMed Abstract: The 9-cis-retinoic acid receptors (RXRalpha, RXRbeta, and RXRgamma) are nuclear receptors that play key roles in multiple hormone-signaling pathways. Biochemical data indicate that, in the absence of ligand, RXR can exist as an inactive tetramer and that its dissociation, induced by ligand, is important for receptor activation. In this article we report the inactivated tetramer structures of the RXRalpha ligand-binding domain (LBD), either in the absence of or in the presence of a nonactivating ligand. These structures reveal that the RXR LBD tetramer forms a compact, disc-shaped complex, consisting of two symmetric dimers that are packed along helices 3 and 11. In each monomer, the AF-2 helix protrudes away from the core domain and spans into the coactivator binding site in the adjacent monomer of the symmetric dimer. In this configuration, the AF-2 helix physically excludes the binding of coactivators and suggests an autorepression mechanism that is mediated by the AF-2 helix within the tetramer. The RXR-tetramer interface is assembled from amino acids that are conserved across several closely related receptors, including the HNF4s and COUP transcription factors, and may therefore provide a model for understanding structure and regulation of this subfamily of nuclear receptors.

PubMed: 10970886
DOI: 10.1101/gad.802300

実験手法

X-RAY DIFFRACTION (2 Å)