7PRX

wildtype ligand binding domain of the glucocorticoid receptor complexed with velsecorat and a PGC1a coactivator fragment

7PRX の概要

• エントリーDOI: 10.2210/pdb7prx/pdb
• 分子名称: Glucocorticoid receptor, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, Velsecorat, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, ligand-activated transcription factor, agonist, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31977.10

構造登録者

Edman, K.,Wissler, L.,Koehler, C.,Postel, S. (登録日: 2021-09-22, 公開日: 2023-02-08, 最終更新日: 2024-02-07)

主引用文献

Postel, S.,Wissler, L.,Johansson, C.A.,Gunnarsson, A.,Gordon, E.,Collins, B.,Castaldo, M.,Kohler, C.,Oling, D.,Johansson, P.,Froderberg Roth, L.,Beinsteiner, B.,Dainty, I.,Delaney, S.,Klaholz, B.P.,Billas, I.M.L.,Edman, K.
Quaternary glucocorticoid receptor structure highlights allosteric interdomain communication.
Nat.Struct.Mol.Biol., 30:286-295, 2023

PubMed Abstract: The glucocorticoid receptor (GR) is a ligand-activated transcription factor that binds DNA and assembles co-regulator complexes to regulate gene transcription. GR agonists are widely prescribed to people with inflammatory and autoimmune diseases. Here we present high-resolution, multidomain structures of GR in complex with ligand, DNA and co-regulator peptide. The structures reveal how the receptor forms an asymmetric dimer on the DNA and provide a detailed view of the domain interactions within and across the two monomers. Hydrogen-deuterium exchange and DNA-binding experiments demonstrate that ligand-dependent structural changes are communicated across the different domains in the full-length receptor. This study demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore, provides a platform to build a new level of understanding of how receptor modifications can drive disease progression and offers key insight for future drug design.

PubMed: 36747092
DOI: 10.1038/s41594-022-00914-4

実験手法

X-RAY DIFFRACTION (2.2 Å)