SASDF64: RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR inverse a...

Basic information

Entry

Database: SASBDB / ID: SASDF64

Sample

RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR inverse agonist (BMS493)

• 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)

Function / homology

Function:

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 / positive regulation of translational initiation by iron / Endogenous sterols / 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 / nuclear thyroid hormone receptor binding / response to vitamin A / limb development / apoptotic cell clearance / regulation of myelination / histone deacetylase regulator activity / Signaling by Retinoic Acid / ureteric bud development / cardiac muscle cell proliferation / nuclear steroid receptor activity / DNA-binding transcription repressor activity / protein kinase A binding / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / ventricular cardiac muscle tissue morphogenesis / heterocyclic compound binding / positive regulation of interleukin-4 production / alpha-actinin binding / face development / locomotor rhythm / germ cell development / negative regulation of type II interferon production / cellular response to Thyroglobulin triiodothyronine / negative regulation of tumor necrosis factor production / regulation of multicellular organism growth / cellular response to estrogen stimulus / epidermis development / establishment of skin barrier / positive regulation of bone mineralization / nuclear retinoid X receptor binding / response to retinoic acid / retinoic acid receptor signaling pathway / heart morphogenesis / cellular response to retinoic acid / positive regulation of cell cycle / hormone-mediated signaling pathway / transcription repressor complex / embryo implantation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of neuron differentiation / response to cytokine / mRNA regulatory element binding translation repressor activity / negative regulation of miRNA transcription / liver development / cholesterol homeostasis / hippocampus development

Domain/homology:

: / : / 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 / Nuclear hormone receptor / Homeobox-like domain superfamily / 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

Component:

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

• Biological species: Mouse (Mus musculus); Human (Homo sapiens)
• Citation: Journal: Structure / Year: 2019; Title: Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression.; Authors: 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 / ; Abstract: 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.

Contact author

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

Models

Sample

• Sample: Name: RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR inverse agonist (BMS493); Specimen concentration: 1.3 mg/ml / Entity id: 1515 / 1536 / 1537
• Buffer: Name: 50mM Tris HCl, 150mM NaCl, 2mM TCEP. / pH: 7.5

Entity #1515

Name: N-CoR-NID / Type: protein
Description: Nuclear receptor CoRepressor 1; Nuclear Receptor Interaction Domain (NID)
Formula weight: 29.139 / Num. of mol.: 1 / Source: Mouse (Mus musculus) / References: UniProt: Q60974
Sequence:

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

Entity #1536

Name: RXR / Type: protein
Description: Retinoid-X receptor alpha (RXR-alpha) Ligand Binding Domain (LBD)
Formula weight: 26.47 / Num. of mol.: 1 / Source: Mouse (Mus musculus) / References: UniProt: P28700
Sequence:

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

Entity #1537

Name: RAR / Type: protein
Description: Retinoic acid receptor alpha (RAR-alpha) Ligand binding domain (LDB)
Formula weight: 28.047 / Num. of mol.: 1 / Source: Human (Homo sapiens) / References: UniProt: P10276
Sequence:

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

Experimental information

• Beam: Instrument name: ESRF BM29 / City: Grenoble / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.099 Å / Dist. spec. to detc.: 2.9 mm
• Detector: Name: Pilatus 1M / Type: Dectris / Pixsize x: 172 mm

Scan

Title: RXR/RAR Heterodimer : N-CoRNID Complex (1:1) with RAR inverse agonist (BMS493)
Measurement date: Jul 23, 2014 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 1 sec. / Number of frames: 10 / Unit: 1/nm /

	Min	Max
Q	0.1781	4.2995

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 800 /

	Min	Max
Q	0.178136	3.96315
P(R) point	1	800
R	0	19.5

Result

Type of curve: single_conc
Comments: BMS493 was added to the complex in a three molar excess before concentration (n.b., BMS493 = (E)-4-[2-[5,6-Dihydro- 5,5-dimethyl - 8- (2-phenylethynyl)naphthalen - 2- yl]ethen - 1- yl]benzoic acid, 4-[(1E)-2-[5,6 -Dihydro -5,5- dimethyl-8- (phenylethynyl)- 2-naphthalenyl]ethenyl]- benzoic acid).

	Experimental	Standard	Porod
MW	83.53 kDa	75.6 kDa	-
Volume	-	-	178 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	75.17	10	72.8	0.32
Radius of gyration, Rg	5.268 nm	0.2	4.75 nm	0.17

	Min	Max	Error
D	-	19.5	1
Guinier point	1	18	-