+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8833 | |||||||||
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タイトル | Mutated BRCA1-BARD1 | |||||||||
マップデータ | Model of BRCA1-BARD1 isolated from the mutated human breast cancer cell line HCC1937 | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / random inactivation of X chromosome / negative regulation of centriole replication / sex-chromosome dosage compensation ...negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / random inactivation of X chromosome / negative regulation of centriole replication / sex-chromosome dosage compensation / negative regulation of intracellular estrogen receptor signaling pathway / gamma-tubulin ring complex / nuclear ubiquitin ligase complex / chordate embryonic development / cellular response to indole-3-methanol / negative regulation of fatty acid biosynthetic process / lateral element / homologous recombination / DNA strand resection involved in replication fork processing / tissue homeostasis / protein K6-linked ubiquitination / regulation of DNA damage checkpoint / regulation of phosphorylation / Impaired BRCA2 binding to PALB2 / XY body / mitotic G2/M transition checkpoint / negative regulation of protein export from nucleus / postreplication repair / DNA repair complex / RNA polymerase binding / centrosome cycle / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / intracellular non-membrane-bounded organelle / HDR through Single Strand Annealing (SSA) / negative regulation of gene expression via chromosomal CpG island methylation / Impaired BRCA2 binding to RAD51 / DNA-binding transcription activator activity / response to ionizing radiation / Transcriptional Regulation by E2F6 / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of cell cycle / positive regulation of vascular endothelial growth factor production / negative regulation of reactive oxygen species metabolic process / positive regulation of DNA repair / protein autoubiquitination / male germ cell nucleus / SUMOylation of DNA damage response and repair proteins / regulation of DNA repair / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / ubiquitin ligase complex / Meiotic synapsis / tubulin binding / Meiotic recombination / Nonhomologous End-Joining (NHEJ) / chromosome segregation / cellular response to ionizing radiation / TP53 Regulates Transcription of DNA Repair Genes / kinase binding / G2/M DNA damage checkpoint / double-strand break repair via homologous recombination / RING-type E3 ubiquitin transferase / HDR through Homologous Recombination (HRR) / negative regulation of cell growth / p53 binding / Metalloprotease DUBs / fatty acid biosynthetic process / cytoplasmic ribonucleoprotein granule / positive regulation of protein catabolic process / positive regulation of angiogenesis / ubiquitin-protein transferase activity / chromosome / intrinsic apoptotic signaling pathway in response to DNA damage / UCH proteinases / KEAP1-NFE2L2 pathway / double-strand break repair / Processing of DNA double-strand break ends / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / cellular response to tumor necrosis factor / Neddylation / Regulation of TP53 Activity through Phosphorylation / transcription coactivator activity / transcription cis-regulatory region binding / damaged DNA binding / nuclear body / regulation of cell cycle / protein ubiquitination / nuclear speck / ribonucleoprotein complex / protein heterodimerization activity / positive regulation of apoptotic process / DNA repair / negative regulation of DNA-templated transcription / DNA damage response / ubiquitin protein ligase binding 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / ネガティブ染色法 / 解像度: 14.7 Å | |||||||||
データ登録者 | Kelly DF / Dearnaley WJ | |||||||||
引用 | ジャーナル: Sci Adv / 年: 2017 タイトル: Structural analysis of BRCA1 reveals modification hotspot. 著者: Yanping Liang / William J Dearnaley / A Cameron Varano / Carly E Winton / Brian L Gilmore / Nick A Alden / Zhi Sheng / Deborah F Kelly / 要旨: Cancer cells afflicted with mutations in the breast cancer susceptibility protein (BRCA1) often suffer from increased DNA damage and genomic instability. The precise manner in which physical changes ...Cancer cells afflicted with mutations in the breast cancer susceptibility protein (BRCA1) often suffer from increased DNA damage and genomic instability. The precise manner in which physical changes to BRCA1 influence its role in DNA maintenance remains unclear. We used single-particle electron microscopy to study the three-dimensional properties of BRCA1 naturally produced in breast cancer cells. Structural studies revealed new information for full-length BRCA1, engaging its nuclear binding partner, the BRCA1-associated RING domain protein (BARD1). Equally important, we identified a region in mutated BRCA1 that was highly susceptible to ubiquitination. We refer to this site as a modification "hotspot." Ubiquitin adducts in the hotspot region proved to be biochemically reversible. Collectively, we show how key changes to BRCA1 affect its structure-function relationship, and present new insights to potentially modulate mutated BRCA1 in human cancer cells. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_8833.map.gz | 711 KB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-8833-v30.xml emd-8833.xml | 10.9 KB 10.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8833.png | 27.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8833 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8833 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_8833_validation.pdf.gz | 78.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_8833_full_validation.pdf.gz | 77.5 KB | 表示 | |
XML形式データ | emd_8833_validation.xml.gz | 495 B | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8833 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8833 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_8833.map.gz / 形式: CCP4 / 大きさ: 844.7 KB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Model of BRCA1-BARD1 isolated from the mutated human breast cancer cell line HCC1937 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 4.4 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Mutated BRCA1-BARD1 complex.
全体 | 名称: Mutated BRCA1-BARD1 complex. |
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要素 |
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-超分子 #1: Mutated BRCA1-BARD1 complex.
超分子 | 名称: Mutated BRCA1-BARD1 complex. / タイプ: complex / ID: 1 / 親要素: 0 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-実験情報
-構造解析
手法 | ネガティブ染色法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 0.02 mg/mL |
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緩衝液 | pH: 7.2 / 構成要素 - 名称: HEPES buffer 詳細: 20 mM HEPES buffer pH 7.2, 150 mM NaCl, 10 mM CaCl2, 10 mM MgCl2 |
染色 | タイプ: NEGATIVE / 材質: Uranyl Formate / 詳細: 1% uranyl formate |
グリッド | モデル: Ted Pella / 材質: COPPER / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: CONTINUOUS / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR |
-電子顕微鏡法
顕微鏡 | FEI TECNAI SPIRIT |
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撮影 | フィルム・検出器のモデル: FEI EAGLE (2k x 2k) / デジタル化 - サンプリング間隔: 30.0 µm / 撮影したグリッド数: 4 / 実像数: 100 / 平均電子線量: 5.0 e/Å2 |
電子線 | 加速電圧: 120 kV / 電子線源: LAB6 |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.0 mm / 最小 デフォーカス(公称値): -1.5 µm / 倍率(公称値): 68000 |
試料ステージ | 試料ホルダーモデル: SIDE ENTRY, EUCENTRIC |
実験機器 | モデル: Tecnai Spirit / 画像提供: FEI Company |