SASDF54: RXRΔH12/RAR Heterodimer : N-CoRNID Complex (1:1)

基本情報

登録情報

データベース: SASBDB / ID: SASDF54

試料

RXRΔH12/RAR Heterodimer : N-CoRNID Complex (1:1)

• Nuclear receptor CoRepressor 1; Nuclear Receptor Interaction Domain (NID) (protein), N-CoR-NID, Mouse (Mus musculus)
• Retinoid-X receptor alpha (RXR-alpha) Ligand Binding Domain (LBD) (protein), RXR, Mouse (Mus musculus)
• Retinoid-X receptor alpha (RXR-alpha) Δ helix12 (protein), RXRΔH12, Mouse (Mus musculus)

機能・相同性

分子機能:

Transcriptional regulation of granulopoiesis / Carnitine shuttle / Transcriptional regulation of white adipocyte differentiation / Signaling by Retinoic Acid / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / definitive erythrocyte differentiation / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / SUMOylation of intracellular receptors / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Recycling of bile acids and salts / Synthesis of bile acids and bile salts / Nuclear Receptor transcription pathway / ventricular cardiac muscle cell differentiation / visceral serous pericardium development / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / mesenchyme development / HDACs deacetylate histones / Endogenous sterols / positive regulation of translational initiation by iron / Notch-HLH transcription pathway / maternal placenta development / Regulation of lipid metabolism by PPARalpha / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / retinoic acid-responsive element binding / Cytoprotection by HMOX1 / thalamus development / positive regulation of thyroid hormone receptor signaling pathway / angiogenesis involved in coronary vascular morphogenesis / cardiac muscle cell differentiation / nuclear retinoic acid receptor binding / camera-type eye development / regulation of thyroid hormone receptor signaling pathway / positive regulation of vitamin D receptor signaling pathway / peroxisome proliferator activated receptor binding / ventricular cardiac muscle tissue morphogenesis / histone deacetylase regulator activity / nuclear thyroid hormone receptor binding / cardiac muscle cell proliferation / regulation of myelination / nuclear steroid receptor activity / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / locomotor rhythm / cellular response to Thyroglobulin triiodothyronine / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of multicellular organism growth / epidermis development / establishment of skin barrier / positive regulation of bone mineralization / retinoic acid receptor signaling pathway / nuclear retinoid X receptor binding / heart morphogenesis / response to retinoic acid / response to glucocorticoid / transcription repressor complex / embryo implantation / hormone-mediated signaling pathway / cholesterol homeostasis / nuclear estrogen receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / circadian regulation of gene expression / mRNA transcription by RNA polymerase II / placenta development / chromatin DNA binding / transcription coactivator binding / histone deacetylase binding / RNA polymerase II transcription regulator complex / nuclear receptor activity / transcription corepressor activity / heart development / chromatin organization / T cell differentiation in thymus / gene expression / in utero embryonic development / transcription regulator complex / sequence-specific DNA binding / cell differentiation / transcription cis-regulatory region binding / protein stabilization / positive regulation of apoptotic process / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein domain specific binding / negative regulation of cell population proliferation / axon / negative regulation of gene expression / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / protein-containing complex binding / chromatin / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / mitochondrion

ドメイン・相同性:

N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Nuclear/hormone receptor activator site AF-1 / Nuclear/hormone receptor activator site AF-1 / Retinoid X receptor/HNF4 / : / SANT domain profile. / SANT domain / Myb domain / Myb-like DNA-binding domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / Homeobox-like domain superfamily / 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

構成要素:

Retinoic acid receptor RXR-alpha / Nuclear receptor corepressor 1

• 生物種: Mouse (Mus musculus)
• 引用: ジャーナル: Structure / 年: 2019; タイトル: Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression.; 著者: Tiago N Cordeiro / Nathalie Sibille / Pierre Germain / Philippe Barthe / Abdelhay Boulahtouf / Fréderic Allemand / Rémy Bailly / Valérie Vivat / Christine Ebel / Alessandro Barducci / William Bourguet / Albane le Maire / Pau Bernadó / ; 要旨: In its unliganded form, the retinoic acid receptor (RAR) in heterodimer with the retinoid X receptor (RXR) exerts a strong repressive activity facilitated by the recruitment of transcriptional corepressors in the promoter region of target genes. By integrating complementary structural, biophysical, and computational information, we demonstrate that intrinsic disorder is a required feature for the precise regulation of RAR activity. We show that structural dynamics of RAR and RXR H12 regions is an essential mechanism for RAR regulation. Unexpectedly we found that, while mainly disordered, the corepressor N-CoR presents evolutionary conserved structured regions involved in transient intramolecular contacts. In the presence of RXR/RAR, N-CoR exploits its multivalency to form a cooperative multisite complex that displays equilibrium between different conformational states that can be tuned by cognate ligands and receptor mutations. This equilibrium is key to preserving the repressive basal state while allowing the conversion to a transcriptionally active form.

登録者

• Tiago Cordeiro (Instituto de Tecnologia Química e Biológica António Xavier, Universidade de Lisboa, Oeiras, Portugal)

モデル

試料

• 試料: 名称: RXRΔH12/RAR Heterodimer : N-CoRNID Complex (1:1) / 試料濃度: 0.80-11.20 / Entity id: 1515 / 1536 / 1538
• バッファ: 名称: 50mM Tris HCl, 150mM NaCl, 2mM TCEP. / pH: 7.5

要素 #1515

名称: N-CoR-NID / タイプ: protein
記述: Nuclear receptor CoRepressor 1; Nuclear Receptor Interaction Domain (NID)
分子量: 29.139 / 分子数: 1 / 由来: Mouse (Mus musculus) / 参照: UniProt: Q60974
配列:

GPHMQVPRTH RLITLADHIC QIITQDFARN QVPSQASTST FQTSPSALSS TPVRTKTSSR YSPESQSQTV LHPRPGPRVS PENLVDKSRG SRPGKSPERS HIPSEPYEPI SPPQGPAVHE KQDSMLLLSQ RGVDPAEQRS DSRSPGSISY LPSFFTKLES TSPMVKSKKQ EIFRKLNSSG GGDSDMAAAQ PGTEIFNLPA VTTSGAVSSR SHSFADPASN LGLEDIIRKA LMGSFDDKVE DHGVVMSHPV GIMPGSASTS VVTSSEARRD E

要素 #1536

名称: RXR / タイプ: protein
記述: Retinoid-X receptor alpha (RXR-alpha) Ligand Binding Domain (LBD)
分子量: 26.47 / 分子数: 1 / 由来: Mouse (Mus musculus) / 参照: UniProt: P28700
配列:

SANEDMPVEK ILEAELAVEP KTETYVEANM GLNPSSPNDP VTNICQAADK QLFTLVEWAK RIPHFSELPL DDQVILLRAG WNELLIASAS HRSIAVKDGI LLATGLHVHR NSAHSAGVGA IFDRVLTELV SKMRDMQMDK TELGCLRAIV LFNPDSKGLS NPAEVEALRE KVYASLEAYC KHKYPEQPGR FAKLLLRLPA LRSIGLKCLE HLFFFKLIGD TPIDTFLMEM LEAPHQAT

要素 #1538

名称: RXRΔH12 / タイプ: protein / 記述: Retinoid-X receptor alpha (RXR-alpha) Δ helix12 / 分子量: 23.5 / 分子数: 1 / 由来: Mouse (Mus musculus) / 参照: UniProt: P28700
配列:

STSSANEDMP VEKILEAELA VEPKTETYVE ANMGLNPSSP NDPVTNICQA ADKQLFTLVE WAKRIPHFSE LPLDDQVILL RAGWNELLIA SASHRSIAVK DGILLATGLH VHRNSAHSAG VGAIFDRVLT ELVSKMRDMQ MDKTELGCLR AIVLFNPDSK GLSNPAEVEA LREKVYASLE AYCKHKYPEQ PGRFAKLLLR LPALRSIGLK CLE

実験情報

• ビーム: 設備名称: ESRF BM29 / 地域: Grenoble / 国: France / 線源: X-ray synchrotron / 波長: 0.099 Å / スペクトロメータ・検出器間距離: 2.9 mm
• 検出器: 名称: Pilatus 1M / タイプ: Dectris / Pixsize x: 172 mm

スキャン

タイトル: RXRΔH12/RAR Heterodimer : N-CoRNID Complex (1:1)
測定日: 2014年7月23日 / 保管温度: 10 °C / セル温度: 10 °C / 照射時間: 1 sec. / フレーム数: 10 / 単位: 1/nm /

	Min	Max
Q	0.1801	4.4504

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 686 /

	Min	Max
Q	0.216983	2.01929
P(R) point	1	686
R	0	15.7

結果

カーブのタイプ: merged /

	実験値	Porod
分子量	79.1 kDa	-
体積	-	183 nm3

	P(R)	Guinier	Guinier error
前方散乱 I0	2715	2794.37	51.2
慣性半径, Rg	4.239 nm	4.24 nm	0.1

	Min	Max
D	-	15.7
Guinier point	12	49