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 shuttle / Transcriptional regulation of white adipocyte differentiation / Signaling by Retinoic Acid / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / definitive erythrocyte differentiation / 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 / 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 / maternal placenta development / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Regulation of lipid metabolism by PPARalpha / Cytoprotection by HMOX1 / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / positive regulation of thyroid hormone receptor signaling pathway / thalamus development / angiogenesis involved in coronary vascular morphogenesis / cardiac muscle cell differentiation / nuclear retinoic acid receptor binding / camera-type eye development / regulation of thyroid hormone receptor signaling pathway / positive regulation of vitamin D receptor signaling pathway / nuclear thyroid hormone receptor binding / 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 / nuclear steroid receptor activity / ventricular cardiac muscle tissue morphogenesis / locomotor rhythm / cellular response to Thyroglobulin triiodothyronine / regulation of multicellular organism growth / epidermis development / establishment of skin barrier / positive regulation of bone mineralization / nuclear retinoid X receptor binding / heart morphogenesis / retinoic acid receptor signaling pathway / hormone-mediated signaling pathway / transcription repressor complex / embryo implantation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cholesterol homeostasis / RNA polymerase II transcription regulatory region sequence-specific DNA binding / placenta development / circadian regulation of gene expression / mRNA transcription by RNA polymerase II / transcription coactivator binding / chromatin DNA binding / RNA polymerase II transcription regulator complex / nuclear receptor activity / transcription corepressor activity / chromatin organization / T cell differentiation in thymus / heart development / gene expression / transcription regulator complex / sequence-specific DNA binding / in utero embryonic development / transcription cis-regulatory region binding / protein stabilization / protein domain specific binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / negative regulation of DNA-templated transcription / chromatin binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / mitochondrion / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm

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. / 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

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 synchrotron / 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