SASDDU8: Multidomain architecture of the estrogen receptor reveals interfa...

基本情報

• 登録情報: データベース: SASBDB / ID: SASDDU8

試料

Multidomain architecture of the estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains

• Estrogen receptor (protein), hERa CDE
• ERE1 (DNA), hERa_ERE1, Homo sapiens
• ERE2 (DNA), hERa_ERE2, Homo sapiens
• Estradiol (other)
• hERa peptide1 (protein)
• hERa peptide2 (protein)

機能・相同性

分子機能:

regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / nuclear estrogen receptor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / epithelial cell proliferation involved in mammary gland duct elongation / prostate epithelial cord elongation / epithelial cell development / negative regulation of smooth muscle cell apoptotic process / uterus development / mammary gland branching involved in pregnancy / vagina development / TFIIB-class transcription factor binding / steroid hormone receptor signaling pathway / androgen metabolic process / cellular response to estrogen stimulus / mammary gland alveolus development / estrogen response element binding / Mitochondrial unfolded protein response (UPRmt) / nuclear receptor-mediated steroid hormone signaling pathway / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / protein localization to chromatin / estrogen receptor signaling pathway / negative regulation of canonical NF-kappaB signal transduction / steroid binding / 14-3-3 protein binding / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / nitric-oxide synthase regulator activity / positive regulation of nitric-oxide synthase activity / negative regulation of miRNA transcription / ESR-mediated signaling / positive regulation of DNA-binding transcription factor activity / transcription coregulator binding / transcription corepressor binding / nuclear estrogen receptor binding / negative regulation of DNA-binding transcription factor activity / stem cell differentiation / SUMOylation of intracellular receptors / cellular response to estradiol stimulus / euchromatin / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / nuclear receptor activity / positive regulation of fibroblast proliferation / male gonad development / Constitutive Signaling by Aberrant PI3K in Cancer / Regulation of RUNX2 expression and activity / sequence-specific double-stranded DNA binding / positive regulation of nitric oxide biosynthetic process / Ovarian tumor domain proteases / response to estradiol / PIP3 activates AKT signaling / ATPase binding / positive regulation of cytosolic calcium ion concentration / DNA-binding transcription activator activity, RNA polymerase II-specific / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / regulation of inflammatory response / fibroblast proliferation / phospholipase C-activating G protein-coupled receptor signaling pathway / transcription regulator complex / Estrogen-dependent gene expression / DNA-binding transcription factor activity, RNA polymerase II-specific / Extra-nuclear estrogen signaling / calmodulin binding / chromatin remodeling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / chromatin binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / protein kinase binding / chromatin / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / Golgi apparatus / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / identical protein binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm

ドメイン・相同性:

Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / : / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type

構成要素:

Estrogen receptor

• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: Nat Commun / 年: 2018; タイトル: Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains.; 著者: Wei Huang / Yi Peng / Janna Kiselar / Xuan Zhao / Aljawharah Albaqami / Daniel Mendez / Yinghua Chen / Srinivas Chakravarthy / Sayan Gupta / Corie Ralston / Hung-Ying Kao / Mark R Chance / Sichun Yang / ; 要旨: Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in several other NRs, but for hERα, the detailed structural architecture of the complex is unknown. By utilizing integrated complementary techniques of small-angle X-ray scattering, hydroxyl radical protein footprinting and computational modeling, here we report an asymmetric L-shaped "boot" structure of the multidomain hERα and identify the specific sites on each domain at the domain interface involved in DBD-LBD interactions. We demonstrate the functional role of the proposed DBD-LBD domain interface through site-specific mutagenesis altering the hERα interfacial structure and allosteric signaling. The L-shaped structure of hERα is a distinctive DBD-LBD organization of NR complexes and more importantly, reveals a signaling mechanism mediated by inter-domain crosstalk that regulates this receptor's allosteric function.

登録者

• Sichun Yang (Case Western Reserve University, Cleveland, USA)

モデル

• モデル #2105: ; タイプ: atomic / カイ2乗値: 1.378276 / P-value: 0.108697; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #2106: ; タイプ: atomic / カイ2乗値: 1.194649 / P-value: 0.389292; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #2107: ; タイプ: atomic / カイ2乗値: 1.245456 / P-value: 0.211077; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: Multidomain architecture of the estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains; 試料濃度: 0.10-0.80 / Entity id: 1139 / 1143 / 1144 / 1145 / 1146 / 1147
• バッファ: 名称: 10 mM CHES (pH9.5), 125 mM NaCl, 5mM KCl, 4 mM MgCl2, 50 mM arginine, 50 mM glutamate, 5 mM TCEP, 5% glycerol, 10 µm Zn acetate, 10 µM estradiol; pH: 9.5

要素 #1139

名称: hERa CDE / タイプ: protein / 記述: Estrogen receptor / 分子量: 42.468 / 分子数: 2 / 参照: UniProt: P03372
配列:

ETRYCAVCND YASGYHYGVW SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC RLRKCYEVGM MKGGIRKDRR GGRMLKHKRQ RDDGEGRGEV GSAGDMRAAN LWPSPLMIKR SKKNSLALSL TADQMVSALL DAEPPILYSE YDPTRPFSEA SMMGLLTNLA DRELVHMINW AKRVPGFVDL TLHDQVHLLE CAWLEILMIG LVWRSMEHPG KLLFAPNLLL DRNQGKCVEG MVEIFDMLLA TSSRFRMMNL QGEEFVCLKS IILLNSGVYT FLSSTLKSLE EKDHIHRVLD KITDTLIHLM AKAGLTLQQQ HQRLAQLLLI LSHIRHMSNK GMEHLYSMKC KNVVPLYDLL LEMLDAHRLH AP

要素 #1143

名称: hERa_ERE1 / タイプ: DNA / 記述: ERE1 / 分子量: 5.909 / 分子数: 1 / 由来: Homo sapiens
配列:

TAGGTACACG TGACCTGCG

要素 #1144

名称: hERa_ERE2 / タイプ: DNA / 記述: ERE2 / 分子量: 5.869 / 分子数: 1 / 由来: Homo sapiens
配列:

CGCAGGTCAC TGTGACCTA

要素 #1145

タイプ: other / 記述: Estradiol / 分子量: 0.272 / 分子数: 2
配列:

C18H24O2

要素 #1146

タイプ: protein / 記述: hERa peptide1 / 分子量: 1.706 / 分子数: 1
配列:

KENALLRYLL DKDD

要素 #1147

タイプ: protein / 記述: hERa peptide2 / 分子量: 1.706 / 分子数: 1
配列:

KENALLRYLL DKDD

実験情報

• ビーム: 設備名称: Advanced Photon Source (APS), Argonne National Laboratory BioCAT 18ID; 地域: Lemont, IL / 国: USA / 線源: X-ray synchrotron / 波長: 0.103 Å / スペクトロメータ・検出器間距離: 3 mm
• 検出器: 名称: MAR 165 CCD

スキャン

タイトル: Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains
測定日: 2014年8月10日 / 保管温度: 4 °C / セル温度: 10 °C / 照射時間: 1.1 sec. / フレーム数: 20 / 単位: 1/A /

	Min	Max
Q	0.0171	0.2468

距離分布関数 P(R)

ソフトウェア P(R): GNOM 4.6 / ポイント数: 59 /

	Min	Max
Q	0.02098	0.2468
P(R) point	1	59
R	0	115

結果

Experimental MW: 98.3 kDa / カーブのタイプ: sec
コメント: Additional SEC parameters: Column type: GE Healthcare Superdex 200 GL 10/300; Flow rate: 0.5 ml/min; Sample injection concentration: 3.5 mg/ml; Injection volume: 500 µl.

	P(R)	Guinier	Guinier error
前方散乱 I0	4.021	4.1	0.04
慣性半径, Rg	3.81 nm	3.8 nm	0.03

	Min	Max
D	-	11.5
Guinier point	1	7