+データを開く
-基本情報
登録情報 | データベース: SASBDB / ID: SASDF77 |
---|---|
試料 | Kinase-inducible domain interacting (KIX) domain of CREB-binding protein tethered to 1-10
|
機能・相同性 | 機能・相同性情報 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 ...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 / 転移酵素; アシル基を移すもの; アミノアシル基以外のアシル基を移すもの / 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 / cellular response to UV / disordered domain specific binding / rhythmic process / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / damaged DNA binding / molecular adaptor activity / transcription coactivator activity / nuclear body / protein domain specific binding / chromatin binding / regulation of DNA-templated transcription / protein-containing complex binding / positive regulation of gene expression / 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 類似検索 - 分子機能 |
生物種 | Mus musculus (ハツカネズミ) |
引用 | ジャーナル: J Biol Chem / 年: 2019 タイトル: Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein. 著者: Archit Garg / Roberto Orru / Weixiang Ye / Ute Distler / Jeremy E Chojnacki / Maja Köhn / Stefan Tenzer / Carsten Sönnichsen / Eva Wolf / 要旨: 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 ...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. |
登録者 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-モデル
モデル #3054 | タイプ: dummy / ダミー原子の半径: 1.75 A / カイ2乗値: 1.215 / P-value: 0.332332 Omokage検索でこの集合体の類似形状データを探す (詳細) |
---|
-試料
試料 | 名称: Kinase-inducible domain interacting (KIX) domain of CREB-binding protein tethered to 1-10 試料濃度: 3.88 mg/ml / Entity id: 1677 / 1681 |
---|---|
バッファ | 名称: 25 mM Hepes, 150 NaCl, 5% Glycerol / pH: 7.2 |
要素 #1677 | 名称: CBP KIX domain / タイプ: protein 記述: Kinase-inducible domain interacting (KIX) domain of CREB-binding protein (CBP), mutation L664C 分子量: 10.476 / 分子数: 1 / 由来: Mus musculus / 参照: UniProt: P45481 配列: GPGVRKGWHE HVTQDLRSHL VHKLVQAIFP TPDPAALKDR RMENLVAYAK KVEGDMYESA NSRDEYYHLL AEKIYKIQKE CEEKRRSRL |
要素 #1681 | 名称: small molecule 1-10 / タイプ: other 記述: 1-{4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidin-1-yl}-3-sulfanylpropan-1-one 分子量: 0.367 / 分子数: 1 配列: C15H17ClF3 NO2S |
-実験情報
ビーム | 設備名称: PETRA III EMBL P12 / 地域: Hamburg / 国: Germany / 線源: X-ray synchrotron / 波長: 0.124 Å / スペクトロメータ・検出器間距離: 3 mm | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
検出器 | 名称: Pilatus 2M | |||||||||||||||||||||
スキャン | タイトル: Kinase-inducible domain interacting (KIX) domain of CREB-binding protein tethered to 1-10 測定日: 2017年5月27日 / 保管温度: 10.2 °C / セル温度: 10.2 °C / 照射時間: 0.045 sec. / フレーム数: 30 / 単位: 1/nm /
| |||||||||||||||||||||
距離分布関数 P(R) | ソフトウェア P(R): GNOM 5.0 / ポイント数: 1660 /
| |||||||||||||||||||||
結果 | Experimental MW: 11.25 kDa / カーブのタイプ: single_conc
|