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 metabolism / Transcriptional regulation of white adipocyte differentiation / Regulation of pyruvate dehydrogenase (PDH) complex / Sertoli cell fate commitment / 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 / positive regulation of binding / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / SUMOylation of intracellular receptors / trachea cartilage development / 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 / HDACs deacetylate histones / mesenchyme development / positive regulation of translational initiation by iron / Endogenous sterols / embryonic camera-type eye development / chondroblast differentiation / Notch-HLH transcription pathway / glandular epithelial cell development / maternal placenta development / negative regulation of granulocyte differentiation / protein kinase B binding / cellular response to corticotropin-releasing hormone stimulus / growth plate cartilage development / positive regulation of T-helper 2 cell differentiation / prostate gland development / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / negative regulation of cartilage development / Regulation of lipid metabolism by PPARalpha / thalamus development / retinoic acid-responsive element binding / regulation of hematopoietic progenitor cell differentiation / Cytoprotection by HMOX1 / positive regulation of thyroid hormone receptor signaling pathway / positive regulation of interleukin-13 production / angiogenesis involved in coronary vascular morphogenesis / positive regulation of interleukin-5 production / nuclear glucocorticoid receptor binding / cardiac muscle cell differentiation / nuclear retinoic acid receptor binding / camera-type eye development / retinoic acid binding / response to vitamin A / positive regulation of vitamin D receptor signaling pathway / regulation of thyroid hormone receptor signaling pathway / peroxisome proliferator activated receptor binding / apoptotic cell clearance / limb development / histone deacetylase regulator activity / nuclear thyroid hormone receptor binding / ventricular cardiac muscle tissue morphogenesis / cardiac muscle cell proliferation / regulation of myelination / protein kinase A binding / ureteric bud development / Signaling by Retinoic Acid / DNA-binding transcription repressor activity / nuclear steroid receptor activity / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / regulation of branching involved in prostate gland morphogenesis / heterocyclic compound binding / positive regulation of interleukin-4 production / face development / alpha-actinin binding / germ cell development / locomotor rhythm / negative regulation of type II interferon production / negative regulation of tumor necrosis factor production / cellular response to Thyroglobulin triiodothyronine / regulation of multicellular organism growth / epidermis development / retinoic acid receptor signaling pathway / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / establishment of skin barrier / cellular response to estrogen stimulus / positive regulation of bone mineralization / positive regulation of cell cycle / nuclear retinoid X receptor binding / heart morphogenesis / cellular response to retinoic acid / response to retinoic acid / response to glucocorticoid / transcription repressor complex / positive regulation of neuron differentiation / embryo implantation / hormone-mediated signaling pathway / mRNA regulatory element binding translation repressor activity / negative regulation of miRNA transcription / liver development / response to cytokine

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. / 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 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