SASDF84: RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR agonist (...

基本情報

登録情報

データベース: SASBDB / ID: SASDF84

試料

RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR agonist (Am580)

• 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)
• Retinoic acid receptor alpha (RAR-alpha) Ligand binding domain (LDB) (protein), RAR, Human (Homo sapiens)

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 / Sertoli cell fate commitment / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / positive regulation of binding / definitive erythrocyte differentiation / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / SUMOylation of intracellular receptors / Downregulation of SMAD2/3:SMAD4 transcriptional activity / trachea cartilage development / Recycling of bile acids and salts / Synthesis of bile acids and bile salts / Nuclear Receptor transcription pathway / visceral serous pericardium development / ventricular cardiac muscle cell differentiation / 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 / chondroblast differentiation / embryonic camera-type eye development / maternal placenta development / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / protein kinase B binding / negative regulation of granulocyte differentiation / growth plate cartilage development / glandular epithelial cell development / positive regulation of T-helper 2 cell differentiation / prostate gland development / Regulation of lipid metabolism by PPARalpha / negative regulation of cartilage development / retinoic acid-responsive element binding / regulation of hematopoietic progenitor cell differentiation / Cytoprotection by HMOX1 / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / positive regulation of thyroid hormone receptor signaling pathway / positive regulation of interleukin-13 production / thalamus development / positive regulation of interleukin-5 production / angiogenesis involved in coronary vascular morphogenesis / cardiac muscle cell differentiation / nuclear retinoic acid receptor binding / outflow tract septum morphogenesis / camera-type eye development / retinoic acid binding / regulation of thyroid hormone receptor signaling pathway / TGFBR3 expression / positive regulation of vitamin D receptor signaling pathway / response to vitamin A / nuclear thyroid hormone receptor binding / limb development / apoptotic cell clearance / regulation of myelination / Signaling by Retinoic Acid / ureteric bud development / histone deacetylase regulator activity / cardiac muscle cell proliferation / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / DNA-binding transcription repressor activity / protein kinase A binding / nuclear steroid receptor activity / ventricular cardiac muscle tissue morphogenesis / heterocyclic compound binding / positive regulation of interleukin-4 production / locomotor rhythm / alpha-actinin binding / face development / germ cell development / negative regulation of type II interferon production / cellular response to Thyroglobulin triiodothyronine / negative regulation of tumor necrosis factor production / cellular response to estrogen stimulus / regulation of multicellular organism growth / epidermis development / establishment of skin barrier / positive regulation of bone mineralization / nuclear retinoid X receptor binding / response to retinoic acid / heart morphogenesis / retinoic acid receptor signaling pathway / cellular response to retinoic acid / positive regulation of cell cycle / hormone-mediated signaling pathway / transcription repressor complex / embryo implantation / response to cytokine / positive regulation of neuron differentiation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / mRNA regulatory element binding translation repressor activity / negative regulation of miRNA transcription / cholesterol homeostasis / liver development / hippocampus development

ドメイン・相同性:

: / : / N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Retinoic acid receptor / Nuclear/hormone receptor activator site AF-1 / Nuclear/hormone receptor activator site AF-1 / Retinoid X receptor/HNF4 / : / SANT domain profile. / Myb domain / SANT 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 / 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:

Retinoic acid receptor alpha / Retinoic acid receptor RXR-alpha / Nuclear receptor corepressor 1

• 生物種: Mouse (Mus musculus); Human (Homo sapiens)
• 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: RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR agonist (Am580); 試料濃度: 0.90-3.50 / Entity id: 1515 / 1536 / 1537
• 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 #1537

名称: RAR / タイプ: protein
記述: Retinoic acid receptor alpha (RAR-alpha) Ligand binding domain (LDB)
分子量: 28.047 / 分子数: 1 / 由来: Human (Homo sapiens) / 参照: UniProt: P10276
配列:

GSHESYTLTP EVGELIEKVR KAHQETFPAL CQLGKYTTNN SSEQRVSLDI DLWDKFSELS TKCIIKTVEF AKQLPGFTTL TIADQITLLK AACLDILILR ICTRYTPEQD TMTFSDGLTL NRTQMHNAGF GPLTDLVFAF ANQLLPLEMD DAETGLLSAI CLICGDRQDL EQPDRVDMLQ EPLLEALKVY VRKRRPSRPH MFPKMLMKIT DLRSISAKGA ERVITLKMEI PGSMPPLIQE MLENSEGLD

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: RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR agonist (Am580)
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	0.1071	4.29

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 693 /

	Min	Max
Q	0.140238	3.41837
P(R) point	1	693
R	0	17.22

結果

カーブのタイプ: merged
コメント: Note: Am580 = 4-[(5,6,7,8-Tetrahydro-5,5,8,8- tetramethyl-2- naphthalenyl) carboxamido]benzoic acid

	実験値	Standard	Standard error	Porod
分子量	83.53 kDa	50.3 kDa	5	82 kDa
体積	-	-	-	131 nm3

	P(R)	Guinier	Guinier error
前方散乱 I0	50.73	51.16	0.14
慣性半径, Rg	4.319 nm	4.24 nm	0.27

	Min	Max
D	-	17.22
Guinier point	9	29