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

Basic information

• Entry: Database: SASBDB / ID: SASDDU8

Sample

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)

Function / homology

Function:

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

Domain/homology:

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 / Zinc finger, C4 type (two domains) / 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

Component:

Estrogen receptor

• Biological species: Homo sapiens (human)
• Citation: Journal: Nat Commun / Year: 2018; Title: Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains.; Authors: 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 / ; Abstract: 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.

Contact author

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

Models

• Model #2105: ; Type: atomic / Chi-square value: 1.378276 / P-value: 0.108697; Search similar-shape structures of this assembly by Omokage search (details)
• Model #2106: ; Type: atomic / Chi-square value: 1.194649 / P-value: 0.389292; Search similar-shape structures of this assembly by Omokage search (details)
• Model #2107: ; Type: atomic / Chi-square value: 1.245456 / P-value: 0.211077; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Multidomain architecture of the estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains; Specimen concentration: 0.10-0.80 / Entity id: 1139 / 1143 / 1144 / 1145 / 1146 / 1147
• Buffer: Name: 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

Entity #1139

Name: hERa CDE / Type: protein / Description: Estrogen receptor / Formula weight: 42.468 / Num. of mol.: 2 / References: UniProt: P03372
Sequence:

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

Entity #1143

Name: hERa_ERE1 / Type: DNA / Description: ERE1 / Formula weight: 5.909 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

TAGGTACACG TGACCTGCG

Entity #1144

Name: hERa_ERE2 / Type: DNA / Description: ERE2 / Formula weight: 5.869 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

CGCAGGTCAC TGTGACCTA

Entity #1145

Type: other / Description: Estradiol / Formula weight: 0.272 / Num. of mol.: 2
Sequence:

C18H24O2

Entity #1146

Type: protein / Description: hERa peptide1 / Formula weight: 1.706 / Num. of mol.: 1
Sequence:

KENALLRYLL DKDD

Entity #1147

Type: protein / Description: hERa peptide2 / Formula weight: 1.706 / Num. of mol.: 1
Sequence:

KENALLRYLL DKDD

Experimental information

• Beam: Instrument name: Advanced Photon Source (APS), Argonne National Laboratory BioCAT 18ID; City: Lemont, IL / 国: USA / Type of source: X-ray synchrotron / Wavelength: 0.103 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: MAR 165 CCD

Scan

Title: Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains
Measurement date: Aug 10, 2014 / Storage temperature: 4 °C / Cell temperature: 10 °C / Exposure time: 1.1 sec. / Number of frames: 20 / Unit: 1/A /

	Min	Max
Q	0.0171	0.2468

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 59 /

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

Result

Experimental MW: 98.3 kDa / Type of curve: sec
Comments: 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
Forward scattering, I0	4.021	4.1	0.04
Radius of gyration, Rg	3.81 nm	3.8 nm	0.03

	Min	Max
D	-	11.5
Guinier point	1	7