SASDF47: Complex of CBP KIX domain with BMAL1 (D530-L625) including C-term...

Basic information

• Entry: Database: SASBDB / ID: SASDF47

Sample

Complex of CBP KIX domain with BMAL1 (D530-L625) including C-terminal transactivation domain (TAD) (Mus musculus)

• Aryl hydrocarbon receptor nuclear translocator-like protein 1 (protein), BMAL1 P624A, Mus musculus
• Kinase-inducible domain interacting (KIX) domain of CREB-binding protein (CBP), mutation L664C (protein), CBP KIX domain, Mus musculus

Function / homology

Function:

Activation of the TFAP2 (AP-2) family of transcription factors / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / Attenuation phase / Regulation of gene expression by Hypoxia-inducible Factor / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / cAMP response element binding protein binding / Formation of the beta-catenin:TCF transactivating complex / NOTCH1 Intracellular Domain Regulates Transcription / RUNX3 regulates NOTCH signaling / Transcriptional and post-translational regulation of MITF-M expression and activity / Notch-HLH transcription pathway / positive regulation of cell adhesion molecule production / germ-line stem cell population maintenance / negative regulation of viral process / Regulation of lipid metabolism by PPARalpha / Cytoprotection by HMOX1 / CD209 (DC-SIGN) signaling / Estrogen-dependent gene expression / peptide lactyltransferase (CoA-dependent) activity / outer kinetochore / negative regulation of interferon-beta production / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / MRF binding / peroxisome proliferator activated receptor binding / face morphogenesis / negative regulation of transcription by RNA polymerase I / peptide-lysine-N-acetyltransferase activity / cellular response to hepatocyte growth factor stimulus / positive regulation of dendritic spine development / acetyltransferase activity / SMAD binding / behavioral response to cocaine / TFIIB-class transcription factor binding / histone acetyltransferase complex / positive regulation of double-strand break repair via homologous recombination / positive regulation of G1/S transition of mitotic cell cycle / long-term memory / histone acetyltransferase activity / histone acetyltransferase / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / RNA polymerase II transcription regulatory region sequence-specific DNA binding / positive regulation of DNA-binding transcription factor activity / protein destabilization / protein modification process / PML body / chromatin DNA binding / cellular response to virus / transcription coactivator binding / RNA polymerase II transcription regulator complex / positive regulation of non-canonical NF-kappaB signal transduction / disordered domain specific binding / cellular response to UV / rhythmic process / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / damaged DNA binding / transcription coactivator activity / molecular adaptor activity / nuclear body / protein domain specific binding / chromatin binding / regulation of DNA-templated transcription / positive regulation of gene expression / protein-containing complex binding / chromatin / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / zinc ion binding / nucleoplasm / nucleus / cytoplasm

Domain/homology:

Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain / CBP/p300-type histone acetyltransferase domain / CBP/p300, atypical RING domain superfamily / KIX domain / CREB-binding protein/p300, atypical RING domain / KIX domain profile. / CBP/p300-type histone acetyltransferase (HAT) domain profile. / Histone acetyltransferase Rtt109/CBP / Histone acetylation protein / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Zinc finger ZZ-type signature. / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ type / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / Nuclear receptor coactivator, interlocking / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type

Component:

Histone lysine acetyltransferase CREBBP / Isoform 2 of Basic helix-loop-helix ARNT-like protein 1

• Biological species: Mus musculus (house mouse)
• Citation: Journal: J Biol Chem / Year: 2019; Title: Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein.; Authors: Archit Garg / Roberto Orru / Weixiang Ye / Ute Distler / Jeremy E Chojnacki / Maja Köhn / Stefan Tenzer / Carsten Sönnichsen / Eva Wolf / ; Abstract: The mammalian CLOCK:BMAL1 transcription factor complex and its coactivators CREB-binding protein (CBP)/p300 and mixed-lineage leukemia 1 (MLL1) critically regulate circadian transcription and chromatin modification. Circadian oscillations are regulated by interactions of BMAL1's C-terminal transactivation domain (TAD) with the KIX domain of CBP/p300 (activating) and with the clock protein CRY1 (repressing) as well as by the BMAL1 G-region preceding the TAD. Circadian acetylation of Lys within the G-region enhances repressive BMAL1-TAD-CRY1 interactions. Here, we characterized the interaction of the CBP-KIX domain with BMAL1 proteins, including the BMAL1-TAD, parts of the G-region, and Lys Tethering the small compound 1-10 in the MLL-binding pocket of the CBP-KIX domain weakened BMAL1 binding, and MLL1-bound KIX did not form a ternary complex with BMAL1, indicating that the MLL-binding pocket is important for KIX-BMAL1 interactions. Small-angle X-ray scattering (SAXS) models of BMAL1 and BMAL1:KIX complexes revealed that the N-terminal BMAL1 G-region including Lys forms elongated extensions emerging from the bulkier BMAL1-TAD:KIX core complex. Fitting high-resolution KIX domain structures into the SAXS-derived envelopes suggested that the G-region emerges near the MLL-binding pocket, further supporting a role of this pocket in BMAL1 binding. Additionally, mutations in the second CREB-pKID/c-Myb-binding pocket of the KIX domain moderately impacted BMAL1 binding. The BMAL1(K537Q) mutation mimicking Lys acetylation, however, did not affect the KIX-binding affinity, in contrast to its enhancing effect on CRY1 binding. Our results significantly advance the mechanistic understanding of the protein interaction networks controlling CLOCK:BMAL1- and CBP-dependent gene regulation in the mammalian circadian clock.

Contact author

• Archit Garg (Institute of Molecular Biology Mainz, Germany)

Models

• Model #3051: ; Type: dummy / Software: (5.3) / Radius of dummy atoms: 2.25 A / Chi-square value: 1.057 / P-value: 0.059199; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Complex of CBP KIX domain with BMAL1 (D530-L625) including C-terminal transactivation domain (TAD) (Mus musculus); Specimen concentration: 2.58 mg/ml / Entity id: 1676 / 1677
• Buffer: Name: 25 mM Hepes, 150 NaCl, 1 mM DTT, 5% Glycerol / pH: 7.2

Entity #1676

Name: BMAL1 P624A / Type: protein
Description: Aryl hydrocarbon receptor nuclear translocator-like protein 1
Formula weight: 9.853 / Num. of mol.: 1 / Source: Mus musculus / References: UniProt: Q9WTL8-2
Sequence:

GPDASSPGGK KILNGGTPDI PSTGLLPGQA QETPGYPYSD SSSILGENPH IGIDMIDNDQ GSSSPSNDEA AMAVIMSLLE ADAGLGGPVD FSDLPWAL

Entity #1677

Name: CBP KIX domain / Type: protein
Description: Kinase-inducible domain interacting (KIX) domain of CREB-binding protein (CBP), mutation L664C
Formula weight: 10.476 / Num. of mol.: 1 / Source: Mus musculus / References: UniProt: P45481
Sequence:

GPGVRKGWHE HVTQDLRSHL VHKLVQAIFP TPDPAALKDR RMENLVAYAK KVEGDMYESA NSRDEYYHLL AEKIYKIQKE CEEKRRSRL

Experimental information

• Beam: Instrument name: PETRA III EMBL P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: Pilatus 2M

Scan

Title: Complex of CBP KIX domain with BMAL1 (D530-L625) including C-terminal transactivation domain (TAD) (Mus musculus)
Measurement date: May 27, 2017 / Storage temperature: 10.3 °C / Cell temperature: 10.4 °C / Exposure time: 0.045 sec. / Number of frames: 30 / Unit: 1/nm /

	Min	Max
Q	0.0474	4.1445

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 1011 /

	Min	Max
Q	0.0968833	2.87414
P(R) point	1	1011
R	0	11.45

Result

Experimental MW: 19.925 kDa / Type of curve: single_conc

	P(R)	Guinier	Guinier error
Forward scattering, I0	5058	4984.25	10.82
Radius of gyration, Rg	2.981 nm	2.78 nm	0.19

	Min	Max
D	-	11.45
Guinier point	19	152