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基本情報
登録情報 | データベース: SASBDB / ID: SASDF37 |
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![]() | KIX domain (kinase-inducible domain interacting domain) of CREB-binding protein (Mus musculus), mutation L664C
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機能・相同性 | ![]() 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 / 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 / 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 / positive regulation of transforming growth factor beta receptor signaling pathway / SMAD binding / non-canonical NF-kappaB signal transduction / behavioral response to cocaine / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() 類似検索 - 分子機能 |
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![]() | ![]() 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. |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
-モデル
モデル #3050 | ![]() タイプ: dummy / ダミー原子の半径: 2.00 A / カイ2乗値: 1.262 / P-value: 0.044939 ![]() |
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試料
![]() | 名称: KIX domain (kinase-inducible domain interacting domain) of CREB-binding protein (Mus musculus), mutation L664C 試料濃度: 5.72 mg/ml |
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バッファ | 名称: 25 mM Hepes, 150 NaCl, 1 mM DTT, 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 |
-実験情報
ビーム | 設備名称: PETRA III EMBL P12 / 地域: Hamburg / 国: Germany ![]() ![]() | |||||||||||||||||||||
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検出器 | 名称: Pilatus 2M | |||||||||||||||||||||
スキャン | 測定日: 2017年5月27日 / 保管温度: 10.3 °C / セル温度: 10.1 °C / 照射時間: 0.045 sec. / フレーム数: 30 / 単位: 1/nm /
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