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

Basic information

Entry

Database: SASBDB / ID: SASDF54

Sample

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)

Function / homology

Function:

Transcriptional regulation of granulopoiesis / Carnitine metabolism / Transcriptional regulation of white adipocyte differentiation / Regulation of pyruvate dehydrogenase (PDH) complex / 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 via 7alpha-hydroxycholesterol / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Nuclear Receptor transcription pathway / Synthesis of bile acids and bile salts / ventricular cardiac muscle cell differentiation / visceral serous pericardium development / mesenchyme development / positive regulation of translational initiation by iron / Endogenous sterols / Notch-HLH transcription pathway / maternal placenta development / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / Regulation of lipid metabolism by PPARalpha / thalamus development / negative regulation of androgen receptor signaling pathway / retinoic acid-responsive element binding / Cytoprotection by HMOX1 / positive regulation of thyroid hormone mediated signaling pathway / angiogenesis involved in coronary vascular morphogenesis / cardiac muscle cell differentiation / nuclear retinoic acid receptor binding / negative regulation of JNK cascade / anatomical structure development / ion binding / camera-type eye development / retinoic acid binding / positive regulation of vitamin D receptor signaling pathway / regulation of thyroid hormone mediated signaling pathway / nuclear vitamin D receptor binding / negative regulation of glycolytic process / peroxisome proliferator activated receptor binding / histone deacetylase regulator activity / nuclear thyroid hormone receptor binding / cardiac muscle cell proliferation / regulation of myelination / ventricular cardiac muscle tissue morphogenesis / DNA binding domain binding / nuclear steroid receptor activity / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / negative regulation of fatty acid metabolic process / LBD domain binding / locomotor rhythm / histone deacetylase complex / cellular response to Thyroglobulin triiodothyronine / regulation of multicellular organism growth / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / spindle assembly / epidermis development / retinoic acid receptor signaling pathway / establishment of skin barrier / positive regulation of bone mineralization / nuclear retinoid X receptor binding / heart morphogenesis / response to retinoic acid / response to glucocorticoid / embryo implantation / peroxisome proliferator activated receptor signaling pathway / transcription repressor complex / hormone-mediated signaling pathway / negative regulation of miRNA transcription / placenta development / cholesterol homeostasis / transcription coregulator binding / nuclear estrogen receptor binding / nuclear receptor binding / peptide binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / circadian regulation of gene expression / mRNA transcription by RNA polymerase II / transcription coactivator binding / mitotic spindle / chromatin DNA binding / histone deacetylase binding / RNA polymerase II transcription regulator complex / transcription corepressor activity / nuclear receptor activity / sequence-specific double-stranded DNA binding / T cell differentiation in thymus / gene expression / chromatin organization / heart development / double-stranded DNA binding / in utero embryonic development / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / sequence-specific DNA binding / cell differentiation

Domain/homology:

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

Component:

Retinoic acid receptor RXR-alpha / Nuclear receptor corepressor 1

• Biological species: Mouse (Mus musculus)
• 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: RXRΔH12/RAR Heterodimer : N-CoRNID Complex (1:1) / Specimen concentration: 0.80-11.20 / Entity id: 1515 / 1536 / 1538
• 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 #1538

Name: RXRΔH12 / Type: protein
Description: Retinoid-X receptor alpha (RXR-alpha) Δ helix12
Formula weight: 23.5 / Num. of mol.: 1 / Source: Mouse (Mus musculus) / References: UniProt: P28700
Sequence:

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

Experimental information

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

Scan

Title: RXRΔH12/RAR Heterodimer : N-CoRNID Complex (1:1) / 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	0.1801	4.4504

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 686 /

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

Result

Type of curve: merged /

	Experimental	Porod
MW	79.1 kDa	-
Volume	-	183 nm3

	P(R)	Guinier	Guinier error
Forward scattering, I0	2715	2794.37	51.2
Radius of gyration, Rg	4.239 nm	4.24 nm	0.1

	Min	Max
D	-	15.7
Guinier point	12	49