4UDC

GR in complex with dexamethasone

4UDC の概要

• エントリーDOI: 10.2210/pdb4udc/pdb
• 関連するPDBエントリー: 4UDA 4UDB 4UDD
• 分子名称: GLUCOCORTICOID RECEPTOR, NUCLEAR RECEPTOR COACTIVATOR 2, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE, ... (5 entities in total)
• 機能のキーワード: signaling protein, nuclear hormone receptor, ligand complex, peptide complex
• 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: 34871.34

構造登録者

Edman, K.,Hogner, A.,Hussein, A.,Bjursell, M.,Aagaard, A.,Backstrom, S.,Bodin, C.,Wissler, L.,Jellesmark-Jensen, T.,Cavallin, A.,Karlsson, U.,Nilsson, E.,Lecina, D.,Takahashi, R.,Grebner, C.,Lepisto, M.,Guallar, V. (登録日: 2014-12-09, 公開日: 2015-11-25, 最終更新日: 2023-12-20)

主引用文献

Edman, K.,Hosseini, A.,Bjursell, M.K.,Aagaard, A.,Wissler, L.,Gunnarsson, A.,Kaminski, T.,Kohler, C.,Backstrom, S.,Jensen, T.J.,Cavallin, A.,Karlsson, U.,Nilsson, E.,Lecina, D.,Takahashi, R.,Grebner, C.,Geschwindner, S.,Lepisto, M.,Hogner, A.C.,Guallar, V.
Ligand Binding Mechanism in Steroid Receptors: From Conserved Plasticity to Differential Evolutionary Constraints.
Structure, 23:2280-, 2015

PubMed Abstract: Steroid receptor drugs have been available for more than half a century, but details of the ligand binding mechanism have remained elusive. We solved X-ray structures of the glucocorticoid and mineralocorticoid receptors to identify a conserved plasticity at the helix 6-7 region that extends the ligand binding pocket toward the receptor surface. Since none of the endogenous ligands exploit this region, we hypothesized that it constitutes an integral part of the binding event. Extensive all-atom unbiased ligand exit and entrance simulations corroborate a ligand binding pathway that gives the observed structural plasticity a key functional role. Kinetic measurements reveal that the receptor residence time correlates with structural rearrangements observed in both structures and simulations. Ultimately, our findings reveal why nature has conserved the capacity to open up this region, and highlight how differences in the details of the ligand entry process result in differential evolutionary constraints across the steroid receptors.

PubMed: 26602186
DOI: 10.1016/J.STR.2015.09.012

実験手法

X-RAY DIFFRACTION (2.5 Å)