6YO8

Binary complex of 14-3-3 zeta with Glucocorticoid Receptor (GR) pT524 peptide

6YO8 の概要

• エントリーDOI: 10.2210/pdb6yo8/pdb
• 分子名称: 14-3-3 protein zeta/delta, Glucocorticoid receptor (3 entities in total)
• 機能のキーワード: 14-3-3 protein zeta/delta, glucocorticoid receptor, protein-peptide complex, protein-protein interaction, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 112719.44

構造登録者

Munier, C.C.,Edman, K.,Perry, M.W.D.,Ottmann, C. (登録日: 2020-04-14, 公開日: 2021-03-24, 最終更新日: 2024-10-23)

主引用文献

Munier, C.C.,De Maria, L.,Edman, K.,Gunnarsson, A.,Longo, M.,MacKintosh, C.,Patel, S.,Snijder, A.,Wissler, L.,Brunsveld, L.,Ottmann, C.,Perry, M.W.D.
Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators.
J.Biol.Chem., 296:100551-100551, 2021

PubMed Abstract: The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein-protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. However, the specific phosphorylation sites on the GR that trigger these interactions and their functional consequences are less clear. Hence, we sought to examine this system in more detail. We used phosphorylated GR peptides, biophysical studies, and X-ray crystallography to identify key residues within the ligand-binding domain of the GR, T524 and S617, whose phosphorylation results in binding of the representative 14-3-3 protein 14-3-3ζ. A kinase screen identified misshapen-like kinase 1 (MINK1) as responsible for phosphorylating T524 and Rho-associated protein kinase 1 for phosphorylating S617; cell-based approaches confirmed the importance of both GR phosphosites and MINK1 but not Rho-associated protein kinase 1 alone in inducing GR-14-3-3 binding. Together our results provide molecular-level insight into 14-3-3-mediated regulation of the GR and highlight both MINK1 and the GR-14-3-3 axis as potential targets for future therapeutic intervention.

PubMed: 33744286
DOI: 10.1016/j.jbc.2021.100551

実験手法

X-RAY DIFFRACTION (2.09 Å)