SASDF74: RXR/RARI396E Heterodimer : N-CoRNID Complex (1:1)

基本情報

登録情報

データベース: SASBDB / ID: SASDF74

試料

RXR/RARI396E 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)
• Retinoic acid receptor alpha (RAR-alpha) Ligand binding domain (LDB) mutant I396E (protein), RARI396E, Human (Homo sapiens)

機能・相同性

分子機能:

Transcriptional regulation of granulopoiesis / Carnitine shuttle / Transcriptional regulation of white adipocyte differentiation / Sertoli cell fate commitment / Signaling by Retinoic Acid / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / positive regulation of binding / 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 / 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 / mesenchyme development / HDACs deacetylate histones / positive regulation of translational initiation by iron / Endogenous sterols / embryonic camera-type eye development / chondroblast differentiation / Notch-HLH transcription pathway / protein kinase B binding / glandular epithelial cell development / maternal placenta development / negative regulation of granulocyte differentiation / growth plate cartilage development / positive regulation of T-helper 2 cell differentiation / prostate gland development / negative regulation of cartilage development / Regulation of lipid metabolism by PPARalpha / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / retinoic acid-responsive element binding / regulation of hematopoietic progenitor cell differentiation / Cytoprotection by HMOX1 / thalamus development / positive regulation of thyroid hormone receptor signaling pathway / angiogenesis involved in coronary vascular morphogenesis / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / cardiac muscle cell differentiation / nuclear retinoic acid receptor binding / camera-type eye development / retinoic acid binding / response to vitamin A / regulation of thyroid hormone receptor signaling pathway / positive regulation of vitamin D receptor signaling pathway / peroxisome proliferator activated receptor binding / apoptotic cell clearance / ventricular cardiac muscle tissue morphogenesis / ureteric bud development / limb development / histone deacetylase regulator activity / nuclear thyroid hormone receptor binding / cardiac muscle cell proliferation / heterocyclic compound binding / Signaling by Retinoic Acid / regulation of myelination / protein kinase A binding / nuclear steroid receptor activity / DNA-binding transcription repressor activity / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / positive regulation of interleukin-4 production / face development / alpha-actinin binding / locomotor rhythm / germ cell development / negative regulation of type II interferon production / cellular response to Thyroglobulin triiodothyronine / negative regulation of tumor necrosis factor production / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of multicellular organism growth / epidermis development / cellular response to estrogen stimulus / positive regulation of cell cycle / 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 / cellular response to retinoic acid / transcription repressor complex / positive regulation of neuron differentiation / embryo implantation / hormone-mediated signaling pathway / mRNA regulatory element binding translation repressor activity / liver development / negative regulation of miRNA transcription / cholesterol homeostasis / response to cytokine / neural tube closure / 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. / 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/RARI396E Heterodimer : N-CoRNID Complex (1:1) / 試料濃度: 0.9 mg/ml / Entity id: 1515 / 1536 / 1540
• 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 #1540

名称: RARI396E / タイプ: protein
記述: Retinoic acid receptor alpha (RAR-alpha) Ligand binding domain (LDB) mutant I396E
分子量: 28.063 / 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 ERVETLKMEI 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: 2.864 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/RARI396E Heterodimer : N-CoRNID Complex (1:1)
測定日: 2015年3月9日 / 保管温度: 10 °C / セル温度: 10 °C / 照射時間: 2 sec. / フレーム数: 10 / 単位: 1/nm /

	Min	Max
Q	0.0859	4.9752

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 486 /

	Min	Max
Q	0.185446	2.48546
P(R) point	1	486
R	0	22.4

結果

カーブのタイプ: single_conc

	実験値	Standard	Standard error	Porod
分子量	85.44 kDa	85.7 kDa	9	-
体積	-	-	-	171 nm3

	P(R)	Guinier	Guinier error
前方散乱 I0	87.75	88.7	0.5
慣性半径, Rg	5.442 nm	5.26 nm	0.1

	Min	Max
D	-	22.4
Guinier point	8	26