- EMDB-17206: Human RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2) complex, 2.2 A resolution -
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IDまたはキーワード:
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基本情報
登録情報
データベース: EMDB / ID: EMD-17206
タイトル
Human RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2) complex, 2.2 A resolution
マップデータ
試料
複合体: RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2)
タンパク質・ペプチド: DNA repair protein RAD51 homolog 2
タンパク質・ペプチド: DNA repair protein RAD51 homolog 3
タンパク質・ペプチド: DNA repair protein RAD51 homolog 4
タンパク質・ペプチド: DNA repair protein XRCC2
リガンド: ADENOSINE-5'-DIPHOSPHATE
リガンド: MAGNESIUM ION
リガンド: ADENOSINE-5'-TRIPHOSPHATE
リガンド: water
キーワード
Complex / ssDNA-binding / ATPase / RAD51 / DNA BINDING PROTEIN
機能・相同性
機能・相同性情報
meiotic DNA recombinase assembly / Rad51C-XRCC3 complex / Rad51B-Rad51C-Rad51D-XRCC2 complex / female meiosis sister chromatid cohesion / blastocyst growth / crossover junction DNA endonuclease activity / somite development / telomere maintenance via recombination / DNA strand invasion / Impaired BRCA2 binding to PALB2 ...meiotic DNA recombinase assembly / Rad51C-XRCC3 complex / Rad51B-Rad51C-Rad51D-XRCC2 complex / female meiosis sister chromatid cohesion / blastocyst growth / crossover junction DNA endonuclease activity / somite development / telomere maintenance via recombination / DNA strand invasion / Impaired BRCA2 binding to PALB2 / gamma-tubulin binding / reciprocal meiotic recombination / regulation of fibroblast apoptotic process / sister chromatid cohesion / 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 / positive regulation of neurogenesis / ATP-dependent DNA damage sensor activity / positive regulation of G2/M transition of mitotic cell cycle / male meiosis I / Presynaptic phase of homologous DNA pairing and strand exchange / response to X-ray / ATP-dependent activity, acting on DNA / neurogenesis / meiotic cell cycle / somitogenesis / interstrand cross-link repair / telomere maintenance / Meiotic recombination / replication fork / TP53 Regulates Transcription of DNA Repair Genes / response to gamma radiation / double-strand break repair via homologous recombination / multicellular organism growth / HDR through Homologous Recombination (HRR) / cell junction / Factors involved in megakaryocyte development and platelet production / double-stranded DNA binding / mitotic cell cycle / single-stranded DNA binding / chromosome, telomeric region / spermatogenesis / DNA recombination / in utero embryonic development / negative regulation of neuron apoptotic process / regulation of cell cycle / intracellular membrane-bounded organelle / DNA repair / centrosome / positive regulation of cell population proliferation / perinuclear region of cytoplasm / ATP hydrolysis activity / mitochondrion / DNA binding / nucleoplasm / ATP binding / nucleus / cytoplasm / cytosol 類似検索 - 分子機能
DNA repair protein XRCC2 / DNA repair protein RAD51 homologue 2 / : / : / : / : / RAD51D, N-terminal domain / DNA recombination and repair protein, RecA-like / DNA recombination and repair protein Rad51-like, C-terminal / Rad51 ...DNA repair protein XRCC2 / DNA repair protein RAD51 homologue 2 / : / : / : / : / RAD51D, N-terminal domain / DNA recombination and repair protein, RecA-like / DNA recombination and repair protein Rad51-like, C-terminal / Rad51 / DNA recombination and repair protein RecA-like, ATP-binding domain / RecA family profile 1. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
DNA repair protein RAD51 homolog 2 / DNA repair protein RAD51 homolog 3 / DNA repair protein XRCC2 / DNA repair protein RAD51 homolog 4 類似検索 - 構成要素
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/W01355X/1
英国
Cancer Research UK
CC2098
英国
Medical Research Council (MRC, United Kingdom)
CC2098
英国
Wellcome Trust
CC2098
英国
European Research Council (ERC)
ERC-ADG-666400
European Union
引用
ジャーナル: Nature / 年: 2023 タイトル: Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor. 著者: Luke A Greenhough / Chih-Chao Liang / Ondrej Belan / Simone Kunzelmann / Sarah Maslen / Monica C Rodrigo-Brenni / Roopesh Anand / Mark Skehel / Simon J Boulton / Stephen C West / 要旨: Homologous recombination is a fundamental process of life. It is required for the protection and restart of broken replication forks, the repair of chromosome breaks and the exchange of genetic ...Homologous recombination is a fundamental process of life. It is required for the protection and restart of broken replication forks, the repair of chromosome breaks and the exchange of genetic material during meiosis. Individuals with mutations in key recombination genes, such as BRCA2 (also known as FANCD1), or the RAD51 paralogues RAD51B, RAD51C (also known as FANCO), RAD51D, XRCC2 (also known as FANCU) and XRCC3, are predisposed to breast, ovarian and prostate cancers and the cancer-prone syndrome Fanconi anaemia. The BRCA2 tumour suppressor protein-the product of BRCA2-is well characterized, but the cellular functions of the RAD51 paralogues remain unclear. Genetic knockouts display growth defects, reduced RAD51 focus formation, spontaneous chromosome abnormalities, sensitivity to PARP inhibitors and replication fork defects, but the precise molecular roles of RAD51 paralogues in fork stability, DNA repair and cancer avoidance remain unknown. Here we used cryo-electron microscopy, AlphaFold2 modelling and structural proteomics to determine the structure of the RAD51B-RAD51C-RAD51D-XRCC2 complex (BCDX2), revealing that RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic. Biochemical and single-molecule analyses showed that BCDX2 stimulates the nucleation and extension of RAD51 filaments-which are essential for recombinational DNA repair-in reactions that depend on the coupled ATPase activities of RAD51B and RAD51C. Our studies demonstrate that BCDX2 orchestrates RAD51 assembly on single stranded DNA for replication fork protection and double strand break repair, in reactions that are critical for tumour avoidance.
名称: RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2) / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 詳細: Recombinant BCDX2 complexes purified from Sf9 insect cells, crosslinked with 0.005% glutaraldehyde (RT, 10 minutes) in the presence of 30 nt ssDNA, and vitrified in the presence of ADP.AlFx. ...詳細: Recombinant BCDX2 complexes purified from Sf9 insect cells, crosslinked with 0.005% glutaraldehyde (RT, 10 minutes) in the presence of 30 nt ssDNA, and vitrified in the presence of ADP.AlFx. THERE IS NO ssDNA BOUND TO BCDX2 IN THIS STRUCTURE
由来(天然)
生物種: Homo sapiens (ヒト)
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分子 #1: DNA repair protein RAD51 homolog 2
分子
名称: DNA repair protein RAD51 homolog 2 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO
詳細: 25 mM HEPES pH 7.5, 100 mM NaCl, 2.5 mM MgCl2, 0.5 mM ADP.AlFx (0.5 mM ADP, 0.5 mM AlCl3, 10 mM NaF), 0.25 mM TCEP, 0.00075% Tween20, 0.075 mM CHAPSO
グリッド
モデル: UltrAuFoil R2/2 / 材質: GOLD / メッシュ: 200 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. / 前処理 - 雰囲気: AIR / 詳細: 45 mA
凍結
凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 277.15 K / 装置: FEI VITROBOT MARK IV
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 35305 / 平均露光時間: 2.78 sec. / 平均電子線量: 53.2 e/Å2
Chain - Source name: PDB / Chain - Initial model type: experimental model
詳細
PDB-8OUY was initially docked into the postprocessed map using ChimeraX 1.4, and iteratively real space refined with Phenix and manually modified using COOT
精密化
空間: REAL / プロトコル: RIGID BODY FIT / 温度因子: 50.38
得られたモデル
PDB-8ouz: Human RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2) complex, 2.2 A resolution