+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 7nht | ||||||
---|---|---|---|---|---|---|---|
タイトル | Akirin2 bound human proteasome | ||||||
![]() |
| ||||||
![]() | TRANSPORT PROTEIN / proteasome / nuclear import | ||||||
機能・相同性 | ![]() proteasome localization / regulation of muscle cell differentiation / positive regulation of B cell activation / nuclear protein quality control by the ubiquitin-proteasome system / positive regulation of adaptive immune response / purine ribonucleoside triphosphate binding / embryo development ending in birth or egg hatching / positive regulation of innate immune response / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly ...proteasome localization / regulation of muscle cell differentiation / positive regulation of B cell activation / nuclear protein quality control by the ubiquitin-proteasome system / positive regulation of adaptive immune response / purine ribonucleoside triphosphate binding / embryo development ending in birth or egg hatching / positive regulation of innate immune response / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome core complex / Somitogenesis / myofibril / NF-kappaB binding / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome assembly / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / immune system process / Regulation of activated PAK-2p34 by proteasome mediated degradation / transcription repressor complex / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / proteasome complex / NIK-->noncanonical NF-kB signaling / SCF-beta-TrCP mediated degradation of Emi1 / proteolysis involved in protein catabolic process / TNFR2 non-canonical NF-kB pathway / AUF1 (hnRNP D0) binds and destabilizes mRNA / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Degradation of DVL / sarcomere / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of AXIN / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / G2/M Checkpoints / Defective CFTR causes cystic fibrosis / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Autodegradation of the E3 ubiquitin ligase COP1 / Negative regulation of NOTCH4 signaling / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / Hedgehog 'on' state / 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 / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / MAPK6/MAPK4 signaling / transcription coregulator activity / Degradation of beta-catenin by the destruction complex / lipopolysaccharide binding / negative regulation of inflammatory response to antigenic stimulus / ABC-family proteins mediated transport / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / P-body / CDK-mediated phosphorylation and removal of Cdc6 / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / Regulation of PTEN stability and activity / cerebral cortex development / Interleukin-1 signaling / Orc1 removal from chromatin / Regulation of RAS by GAPs / positive regulation of interleukin-6 production / response to virus / Regulation of RUNX2 expression and activity / nuclear matrix / The role of GTSE1 in G2/M progression after G2 checkpoint / Separation of Sister Chromatids / KEAP1-NFE2L2 pathway / UCH proteinases / protein import into nucleus / Downstream TCR signaling / Antigen processing: Ubiquitination & Proteasome degradation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / peptidase activity / ER-Phagosome pathway / response to oxidative stress / regulation of inflammatory response / secretory granule lumen / protein-macromolecule adaptor activity / response to lipopolysaccharide / endopeptidase activity / adaptive immune response / proteasome-mediated ubiquitin-dependent protein catabolic process / ficolin-1-rich granule lumen / positive regulation of canonical NF-kappaB signal transduction 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: 3.2 Å | ||||||
![]() | Singh, K. / Brunner, H. / Grishkovskaya, I. / de Almeida, M. / Hinterndorfer, M. / Zuber, J. / Haselbach, D. | ||||||
![]() | ![]() タイトル: AKIRIN2 controls the nuclear import of proteasomes in vertebrates. 著者: Melanie de Almeida / Matthias Hinterndorfer / Hanna Brunner / Irina Grishkovskaya / Kashish Singh / Alexander Schleiffer / Julian Jude / Sumit Deswal / Robert Kalis / Milica Vunjak / Thomas ...著者: Melanie de Almeida / Matthias Hinterndorfer / Hanna Brunner / Irina Grishkovskaya / Kashish Singh / Alexander Schleiffer / Julian Jude / Sumit Deswal / Robert Kalis / Milica Vunjak / Thomas Lendl / Richard Imre / Elisabeth Roitinger / Tobias Neumann / Susanne Kandolf / Michael Schutzbier / Karl Mechtler / Gijs A Versteeg / David Haselbach / Johannes Zuber / ![]() ![]() ![]() ![]() 要旨: Protein expression and turnover are controlled through a complex interplay of transcriptional, post-transcriptional and post-translational mechanisms to enable spatial and temporal regulation of ...Protein expression and turnover are controlled through a complex interplay of transcriptional, post-transcriptional and post-translational mechanisms to enable spatial and temporal regulation of cellular processes. To systematically elucidate such gene regulatory networks, we developed a CRISPR screening assay based on time-controlled Cas9 mutagenesis, intracellular immunostaining and fluorescence-activated cell sorting that enables the identification of regulatory factors independent of their effects on cellular fitness. We pioneered this approach by systematically probing the regulation of the transcription factor MYC, a master regulator of cell growth. Our screens uncover a highly conserved protein, AKIRIN2, that is essentially required for nuclear protein degradation. We found that AKIRIN2 forms homodimers that directly bind to fully assembled 20S proteasomes to mediate their nuclear import. During mitosis, proteasomes are excluded from condensing chromatin and re-imported into newly formed daughter nuclei in a highly dynamic, AKIRIN2-dependent process. Cells undergoing mitosis in the absence of AKIRIN2 become devoid of nuclear proteasomes, rapidly causing accumulation of MYC and other nuclear proteins. Collectively, our study reveals a dedicated pathway controlling the nuclear import of proteasomes in vertebrates and establishes a scalable approach to decipher regulators in essential cellular processes. | ||||||
履歴 |
|
-
構造の表示
ムービー |
![]() |
---|---|
構造ビューア | 分子: ![]() ![]() |
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 570.9 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 450.1 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 | ![]() | 784 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 819.2 KB | 表示 | |
XML形式データ | ![]() | 80.4 KB | 表示 | |
CIF形式データ | ![]() | 127.1 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 | ![]() 12341MC C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
---|---|
類似構造データ | |
電子顕微鏡画像生データ | ![]() Data size: 2.0 TB Data #1: Unaligned Multiframe micrographs of Akirin2 bound to the human proteasome [micrographs - multiframe] Data #2: Motion corrected files dose weighted and summed as well as without dose weigthening [micrographs - single frame] Data #3: Extracted particles of an Akirin2 bound proteasome [picked particles - single frame - processed]) |
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
-Proteasome subunit alpha type- ... , 7種, 7分子 ABCDEFG
#1: タンパク質 | 分子量: 25927.535 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
---|---|
#2: タンパク質 | 分子量: 29525.842 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#3: タンパク質 | 分子量: 27929.891 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#4: タンパク質 | 分子量: 26435.977 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#5: タンパク質 | 分子量: 29595.627 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#6: タンパク質 | 分子量: 28469.252 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#7: タンパク質 | 分子量: 27432.459 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-Proteasome subunit beta type- ... , 7種, 7分子 HIJKLMN
#8: タンパク質 | 分子量: 30000.418 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
---|---|
#9: タンパク質 | 分子量: 22972.896 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#10: タンパク質 | 分子量: 22864.277 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#11: タンパク質 | 分子量: 28510.248 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#12: タンパク質 | 分子量: 26522.396 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#13: タンパク質 | 分子量: 29231.178 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#14: タンパク質 | 分子量: 25377.652 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-タンパク質 / 非ポリマー , 2種, 5分子 cd

#15: タンパク質 | 分子量: 22525.582 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #16: 化合物 | |
---|
-詳細
研究の焦点であるリガンドがあるか | N |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 |
-
試料調製
構成要素 |
| ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 値: 0.78 MDa / 実験値: YES | ||||||||||||||||||||||||||||||
由来(天然) |
| ||||||||||||||||||||||||||||||
由来(組換発現) |
| ||||||||||||||||||||||||||||||
緩衝液 | pH: 6.5 | ||||||||||||||||||||||||||||||
緩衝液成分 |
| ||||||||||||||||||||||||||||||
試料 | 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: COPPER / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R3.5/1 | ||||||||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 81000 X / アライメント法: ZEMLIN TABLEAU |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 1 sec. / 電子線照射量: 33 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: 4595 |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
-
解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア |
| ||||||||||||||||||||||||||||||||||||
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: 1427356 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 37447 / アルゴリズム: FOURIER SPACE / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: RECIPROCAL | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 5LE5 Accession code: 5LE5 / Source name: PDB / タイプ: experimental model | ||||||||||||||||||||||||||||||||||||
精密化 | 解像度: 3.2→3.2 Å / Cor.coef. Fo:Fc: 0.929 / SU B: 8.555 / SU ML: 0.153 / ESU R: 0.284 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| ||||||||||||||||||||||||||||||||||||
溶媒の処理 | イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK | ||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 89.953 Å2
| ||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 合計: 24956 | ||||||||||||||||||||||||||||||||||||
拘束条件 |
| ||||||||||||||||||||||||||||||||||||
LS精密化 シェル | 解像度: 2.8→2.873 Å / Total num. of bins used: 20
|