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基本情報
登録情報 | データベース: PDB / ID: 9cb3 | |||||||||
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タイトル | E2F1-Cyclin F Interface | |||||||||
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![]() | CELL CYCLE / SCF Ubiquitin Ligase | |||||||||
機能・相同性 | ![]() negative regulation of centrosome duplication / negative regulation of fat cell proliferation / Rb-E2F complex / re-entry into mitotic cell cycle / lens fiber cell apoptotic process / F-box domain binding / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / PcG protein complex / anaphase-promoting complex binding / positive regulation of ubiquitin protein ligase activity ...negative regulation of centrosome duplication / negative regulation of fat cell proliferation / Rb-E2F complex / re-entry into mitotic cell cycle / lens fiber cell apoptotic process / F-box domain binding / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / PcG protein complex / anaphase-promoting complex binding / positive regulation of ubiquitin protein ligase activity / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Cul7-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / mRNA stabilization / Transcription of E2F targets under negative control by DREAM complex / Activation of NOXA and translocation to mitochondria / anoikis / negative regulation of DNA binding / Activation of PUMA and translocation to mitochondria / cyclin-dependent protein serine/threonine kinase regulator activity / SCF ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / DNA-binding transcription activator activity / ubiquitin ligase complex scaffold activity / negative regulation of fat cell differentiation / G2 Phase / Prolactin receptor signaling / G1/S-Specific Transcription / Transcriptional Regulation by E2F6 / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / microtubule organizing center / regulation of G1/S transition of mitotic cell cycle / cullin family protein binding / intrinsic apoptotic signaling pathway by p53 class mediator / protein monoubiquitination / ubiquitin-like ligase-substrate adaptor activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / protein K48-linked ubiquitination / Cyclin E associated events during G1/S transition / forebrain development / Cyclin A:Cdk2-associated events at S phase entry / cis-regulatory region sequence-specific DNA binding / cyclin-dependent protein kinase holoenzyme complex / Nuclear events stimulated by ALK signaling in cancer / centriole / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / DNA damage checkpoint signaling / molecular function activator activity / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / placenta development / Dectin-1 mediated noncanonical NF-kB signaling / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Iron uptake and transport / Negative regulation of NOTCH4 signaling / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / beta-catenin binding / Degradation of beta-catenin by the destruction complex / Oncogene Induced Senescence / NOTCH1 Intracellular Domain Regulates Transcription / Pre-NOTCH Transcription and Translation / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / G1/S transition of mitotic cell cycle / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / RNA polymerase II transcription regulator complex / FCERI mediated NF-kB activation / Transcriptional regulation of granulopoiesis / Interleukin-1 signaling / Orc1 removal from chromatin / positive regulation of fibroblast proliferation / protein polyubiquitination / intrinsic apoptotic signaling pathway in response to DNA damage / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / sequence-specific double-stranded DNA binding / : / cellular response to xenobiotic stimulus / Regulation of PLK1 Activity at G2/M Transition / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / Neddylation / Oxidative Stress Induced Senescence / molecular adaptor activity / response to lipopolysaccharide / DNA-binding transcription factor binding / sequence-specific DNA binding / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor activity, RNA polymerase II-specific / regulation of cell cycle / protein dimerization activity / protein ubiquitination 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.47 Å | |||||||||
![]() | Ngoi, P. / Serrao, V.H. / Rubin, S.M. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural mechanism for the recognition of E2F1 by the ubiquitin ligase adaptor Cyclin F. 著者: Peter Ngoi / Xianxi Wang / Sivasankar Putta / Ricardo F Da Luz / Vitor Hugo B Serrão / Michael J Emanuele / Seth M Rubin / ![]() 要旨: Cyclin F, a noncanonical member of the cyclin protein family, plays a critical role in regulating transitions in the cell division cycle. Unlike canonical cyclins, which bind and activate cyclin- ...Cyclin F, a noncanonical member of the cyclin protein family, plays a critical role in regulating transitions in the cell division cycle. Unlike canonical cyclins, which bind and activate cyclin-dependent kinases (CDKs), Cyclin F functions as a substrate receptor protein within the Skp1-Cullin-F-box E3 ubiquitin ligase complex, enabling the ubiquitylation of target proteins. The structural features that distinguish Cyclin F as a ligase adaptor and the mechanisms underlying its selective substrate recruitment over Cyclin A, which functions in complex with CDK2 at a similar time in the cell cycle, remain largely unexplored. We utilized single-particle cryoelectron microscopy to elucidate the structure of a Cyclin F-Skp1 complex bound to an E2F1 peptide. The structure and biochemical analysis reveal important differences in the substrate-binding site of Cyclin F compared to Cyclin A. Our findings expand on the canonical cyclin-binding motif (Cy or RxL) and highlight the importance of electrostatics at the E2F1 binding interface, which varies between Cyclin F and Cyclin A. These results advance our understanding of E2F1 regulation and may inform strategies for selectively targeting Cyclin F in cancer or neurodegeneration. | |||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 130.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 95.2 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 34.9 KB | 表示 | |
CIF形式データ | ![]() | 51.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 45413MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 71695.984 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P41002 |
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#2: タンパク質 | 分子量: 18679.965 Da / 分子数: 1 / Fragment: BTB domain (UNP residues 7-128) / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P63208 |
#3: タンパク質・ペプチド | 分子量: 1540.810 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
Has protein modification | N |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: E2F1-CyclinF-Skp1 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | ||||||||||||||||||||
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分子量 | 値: 0.09176483 MDa / 実験値: NO | ||||||||||||||||||||
由来(天然) | 生物種: ![]() | ||||||||||||||||||||
由来(組換発現) | 生物種: ![]() ![]() | ||||||||||||||||||||
緩衝液 | pH: 8 | ||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 295 K |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: TFS KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 500 nm |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 0.57 sec. / 電子線照射量: 45.8 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 7611 |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 7781999 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.47 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 103503 / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 177 / プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||||||||||||||
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精密化 | 交差検証法: NONE |