[English] 日本語
Yorodumi- SASDDU8: Multidomain architecture of the estrogen receptor reveals interfa... -
+Open data
-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
|
Function / homology | Function and homology information 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 / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation ...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 / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / prostate epithelial cord elongation / epithelial cell development / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / androgen metabolic process / TFIIB-class transcription factor binding / steroid hormone mediated signaling pathway / mammary gland alveolus development / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / estrogen response element binding / positive regulation of phospholipase C activity / intracellular steroid hormone receptor signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / protein localization to chromatin / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / steroid binding / nitric-oxide synthase regulator activity / ESR-mediated signaling / 14-3-3 protein binding / transcription corepressor binding / negative regulation of miRNA transcription / cellular response to estradiol stimulus / nuclear estrogen receptor binding / transcription coregulator binding / stem cell differentiation / positive regulation of nitric-oxide synthase activity / euchromatin / SUMOylation of intracellular receptors / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / male gonad development / Regulation of RUNX2 expression and activity / Constitutive Signaling by Aberrant PI3K in Cancer / positive regulation of nitric oxide biosynthetic process / nuclear receptor activity / positive regulation of DNA-binding transcription factor activity / positive regulation of fibroblast proliferation / Ovarian tumor domain proteases / sequence-specific double-stranded DNA binding / response to estradiol / PIP3 activates AKT signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / 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 / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / chromatin binding / chromatin / regulation of DNA-templated transcription / 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 / membrane / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function |
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) ...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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Data source
SASBDB page | SASDDU8 |
---|
-Related structure data
Similar structure data |
---|
-External links
Related items in Molecule of the Month |
---|
-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 ...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 synchrotronSynchrotron / 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 /
| |||||||||||||||||||||
Distance distribution function P(R) | Sofotware P(R): GNOM 4.6 / Number of points: 59 /
| |||||||||||||||||||||
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.
|