2AA7

Mineralocorticoid Receptor with Bound Deoxycorticosterone

2AA7 の概要

• エントリーDOI: 10.2210/pdb2aa7/pdb
• 関連するPDBエントリー: 2AA2 2AA5 2AA6 2AAX 2AB2
• 分子名称: Mineralocorticoid receptor, SULFATE ION, DESOXYCORTICOSTERONE, ... (5 entities in total)
• 機能のキーワード: mineralocorticoid receptor, mr, nuclear receptor, steroid receptor, deoxycorticosterone, hypertension, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P08235
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32221.23

構造登録者

Bledsoe, R.K.,Madauss, K.P.,Holt, J.A.,Apolito, C.J.,Lambert, M.H.,Pearce, K.H.,Stanley, T.B.,Stewart, E.L.,Trump, R.P.,Willson, T.M.,Williams, S.P. (登録日: 2005-07-13, 公開日: 2005-07-26, 最終更新日: 2024-02-14)

主引用文献

Bledsoe, R.K.,Madauss, K.P.,Holt, J.A.,Apolito, C.J.,Lambert, M.H.,Pearce, K.H.,Stanley, T.B.,Stewart, E.L.,Trump, R.P.,Willson, T.M.,Williams, S.P.
A Ligand-mediated Hydrogen Bond Network Required for the Activation of the Mineralocorticoid Receptor
J.Biol.Chem., 280:31283-31293, 2005

PubMed Abstract: Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

PubMed: 15967794
DOI: 10.1074/jbc.M504098200

実験手法

X-RAY DIFFRACTION (2.2 Å)