2A3I

Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor

2A3I の概要

• エントリーDOI: 10.2210/pdb2a3i/pdb
• 分子名称: Mineralocorticoid receptor, Nuclear receptor coactivator 1, residues 1430-1441, CORTICOSTERONE, ... (4 entities in total)
• 機能のキーワード: transcription factor, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P08235; Nucleus : Q15788
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31236.22

構造登録者

Li, Y.,Suino, K.,Daugherty, J.,Xu, H.E. (登録日: 2005-06-24, 公開日: 2005-07-19, 最終更新日: 2024-02-14)

主引用文献

Li, Y.,Suino, K.,Daugherty, J.,Xu, H.E.
Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor
Mol.Cell, 19:367-380, 2005

PubMed Abstract: Mineralocorticoid receptor (MR) controls sodium homeostasis and blood pressure through hormone binding and coactivator recruitment. Here, we report a 1.95 A crystal structure of the MR ligand binding domain containing a single C808S mutation bound to corticosterone and the fourth LXXLL motif of steroid receptor coactivator-1 (SRC1-4). Through a combination of biochemical and structural analyses, we demonstrate that SRC1-4 is the most potent MR binding motif and mutations that disrupt the MR/SRC1-4 interactions abolish the ability of the full-length SRC1 to coactivate MR. The structure also reveals a compact steroid binding pocket with a unique topology that is primarily defined by key residues of helices 6 and 7. Mutations swapping a single residue at position 848 from helix H7 between MR and glucocorticoid receptor (GR) switch their hormone specificity. Together, these findings provide critical insights into the molecular basis of hormone binding and coactivator recognition by MR and related steroid receptors.

PubMed: 16061183
DOI: 10.1016/j.molcel.2005.06.026

実験手法

X-RAY DIFFRACTION (1.95 Å)