+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36133 | |||||||||
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タイトル | Structure of CRL2APPBP2 bound with RxxGPAA degron (tetramer) | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | E3 Ubiquitination ligase / PROTEIN BINDING (タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / target-directed miRNA degradation / elongin complex / VCB complex ...cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / microtubule associated complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF複合体 / Cul2-RING ubiquitin ligase complex / microtubule motor activity / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / intracellular transport / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / Nuclear events stimulated by ALK signaling in cancer / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / positive regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / Regulation of BACH1 activity / T細胞 / post-translational protein modification / intrinsic apoptotic signaling pathway / transcription corepressor binding / Degradation of DVL / transcription elongation by RNA polymerase II / transcription initiation at RNA polymerase II promoter / Recognition of DNA damage by PCNA-containing replication complex / cellular response to amino acid stimulus / TP53 Regulates Transcription of DNA Repair Genes / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / intracellular protein transport / Hedgehog 'on' state / G1/S transition of mitotic cell cycle / DNA Damage Recognition in GG-NER / 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 / RING-type E3 ubiquitin transferase / Degradation of beta-catenin by the destruction complex / cytoplasmic vesicle membrane / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / negative regulation of canonical Wnt signaling pathway / Inactivation of CSF3 (G-CSF) signaling / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / NOTCH1 Intracellular Domain Regulates Transcription / Formation of TC-NER Pre-Incision Complex / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / protein polyubiquitination / Orc1 removal from chromatin / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / ubiquitin-protein transferase activity / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / cellular response to UV / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / 分裂促進因子活性化タンパク質キナーゼ / protein-macromolecule adaptor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / ubiquitin-dependent protein catabolic process / 精子形成 / proteasome-mediated ubiquitin-dependent protein catabolic process / protein-containing complex assembly 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.54 Å | |||||||||
データ登録者 | Zhao S / Zhang K / Xu C | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: Molecular basis for C-degron recognition by CRL2 ubiquitin ligase. 著者: Shidong Zhao / Diana Olmayev-Yaakobov / Wenwen Ru / Shanshan Li / Xinyan Chen / Jiahai Zhang / Xuebiao Yao / Itay Koren / Kaiming Zhang / Chao Xu / 要旨: E3 ubiquitin ligases determine the specificity of eukaryotic protein degradation by selective binding to destabilizing protein motifs, termed degrons, in substrates for ubiquitin-mediated proteolysis. ...E3 ubiquitin ligases determine the specificity of eukaryotic protein degradation by selective binding to destabilizing protein motifs, termed degrons, in substrates for ubiquitin-mediated proteolysis. The exposed C-terminal residues of proteins can act as C-degrons that are recognized by distinct substrate receptors (SRs) as part of dedicated cullin-RING E3 ubiquitin ligase (CRL) complexes. APPBP2, an SR of Cullin 2-RING ligase (CRL2), has been shown to recognize R-x-x-G/C-degron; however, the molecular mechanism of recognition remains elusive. By solving several cryogenic electron microscopy structures of active CRL2 bound with different R-x-x-G/C-degrons, we unveiled the molecular mechanisms underlying the assembly of the CRL2 dimer and tetramer, as well as C-degron recognition. The structural study, complemented by binding experiments and cell-based assays, demonstrates that APPBP2 specifically recognizes the R-x-x-G/C-degron via a bipartite mechanism; arginine and glycine, which play critical roles in C-degron recognition, accommodate distinct pockets that are spaced by two residues. In addition, the binding pocket is deep enough to enable the interaction of APPBP2 with the motif placed at or up to three residues upstream of the C-end. Overall, our study not only provides structural insight into CRL2-mediated protein turnover but also serves as the basis for future structure-based chemical probe design. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_36133.map.gz | 483.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36133-v30.xml emd-36133.xml | 20.2 KB 20.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_36133.png | 121.2 KB | ||
Filedesc metadata | emd-36133.cif.gz | 6.7 KB | ||
その他 | emd_36133_half_map_1.map.gz emd_36133_half_map_2.map.gz | 475.6 MB 475.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36133 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36133 | 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_36133.map.gz / 形式: CCP4 / 大きさ: 512 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.82 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_36133_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_36133_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : CRL2APPBP2 E3 liganse
全体 | 名称: CRL2APPBP2 E3 liganse |
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要素 |
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-超分子 #1: CRL2APPBP2 E3 liganse
超分子 | 名称: CRL2APPBP2 E3 liganse / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 400 kDa/nm |
-分子 #1: Amyloid protein-binding protein 2
分子 | 名称: Amyloid protein-binding protein 2 / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 66.945258 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MAAVELEWIP ETLYNTAISA VVDNYIRSRR DIRSLPENIQ FDVYYKLYQQ GRLCQLGSEF CELEVFAKVL RALDKRHLLH HCFQALMDH GVKVASVLAY SFSRRCSYIA ESDAAVKEKA IQVGFVLGGF LSDAGWYSDA EKVFLSCLQL CTLHDEMLHW F RAVECCVR ...文字列: MAAVELEWIP ETLYNTAISA VVDNYIRSRR DIRSLPENIQ FDVYYKLYQQ GRLCQLGSEF CELEVFAKVL RALDKRHLLH HCFQALMDH GVKVASVLAY SFSRRCSYIA ESDAAVKEKA IQVGFVLGGF LSDAGWYSDA EKVFLSCLQL CTLHDEMLHW F RAVECCVR LLHVRNGNCK YHLGEETFKL AQTYMDKLSK HGQQANKAAL YGELCALLFA KSHYDEAYKW CIEAMKEITA GL PVKVVVD VLRQASKACV VKREFKKAEQ LIKHAVYLAR DHFGSKHPKY SDTLLDYGFY LLNVDNICQS VAIYQAALDI RQS VFGGKN IHVATAHEDL AYSSYVHQYS SGKFDNALFH AERAIGIITH ILPEDHLLLA SSKRVKALIL EEIAIDCHNK ETEQ RLLQE AHDLHLSSLQ LAKKAFGEFN VQTAKHYGNL GRLYQSMRKF KEAEEMHIKA IQIKEQLLGQ EDYEVALSVG HLASL YNYD MNQYENAEKL YLRSIAIGKK LFGEGYSGLE YDYRGLIKLY NSIGNYEKVF EYHNVLSNWN RLRDRQYSVT DALEDV STS PQSTEEVVQS FLISQNVEGP SC UniProtKB: Amyloid protein-binding protein 2 |
-分子 #2: Cullin-2
分子 | 名称: Cullin-2 / タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 87.068836 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: TSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE TKIFLENHVR HLHKRVLESE EQVLVMYHR YWEEYSKGAD YMDCLYRYLN TQFIKKNKLT EADLQYGYGG VDMNEPLMEI GELALDMWRK LMVEPLQAIL I RMLLREIK ...文字列: TSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE TKIFLENHVR HLHKRVLESE EQVLVMYHR YWEEYSKGAD YMDCLYRYLN TQFIKKNKLT EADLQYGYGG VDMNEPLMEI GELALDMWRK LMVEPLQAIL I RMLLREIK NDRGGEDPNQ KVIHGVINSF VHVEQYKKKF PLKFYQEIFE SPFLTETGEY YKQEASNLLQ ESNCSQYMEK VL GRLKDEE IRCRKYLHPS SYTKVIHECQ QRMVADHLQF LHAECHNIIR QEKKNDMANM YVLLRAVSTG LPHMIQELQN HIH DEGLRA TSNLTQENMP TLFVESVLEV HGKFVQLINT VLNGDQHFMS ALDKALTSVV NYREPKSVCK APELLAKYCD NLLK KSAKG MTENEVEDRL TSFITVFKYI DDKDVFQKFY ARMLAKRLIH GLSMSMDSEE AMINKLKQAC GYEFTSKLHR MYTDM SVSA DLNNKFNNFI KNQDTVIDLG ISFQIYVLQA GAWPLTQAPS STFAIPQELE KSVQMFELFY SQHFSGRKLT WLHYLC TGE VKMNYLGKPY VAMVTTYQMA VLLAFNNSET VSYKELQDST QMNEKELTKT IKSLLDVKMI NHDSEKEDID AESSFSL NM NFSSKRTKFK ITTSMQKDTP QEMEQTRSAV DEDRKMYLQA AIVRIMKARK VLRHNALIQE VISQSRARFN PSISMIKK C IEVLIDKQYI ERSQASADEY SYVA UniProtKB: Cullin-2 |
-分子 #3: Elongin-B
分子 | 名称: Elongin-B / タイプ: protein_or_peptide / ID: 3 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 13.147781 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MDVFLMIRRH KTTIFTDAKE SSTVFELKRI VEGILKRPPD EQRLYKDDQL LDDGKTLGEC GFTSQTARPQ APATVGLAFR ADDTFEALC IEPFSSPPEL PDVMKPQDSG SSANEQAVQ UniProtKB: Elongin-B |
-分子 #4: Elongin-C
分子 | 名称: Elongin-C / タイプ: protein_or_peptide / ID: 4 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 10.84342 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MYVKLISSDG HEFIVKREHA LTSGTIKAML SGPGQFAENE TNEVNFREIP SHVLSKVCMY FTYKVRYTNS STEIPEFPIA PEIALELLM AANFLDC UniProtKB: Elongin-C |
-分子 #5: SUMO-XP_211896+AA C-degron
分子 | 名称: SUMO-XP_211896+AA C-degron / タイプ: protein_or_peptide / ID: 5 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 1.91323 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: TVPTLTRGRL TRNKGPAA |
-分子 #6: E3 ubiquitin-protein ligase RBX1, N-terminally processed
分子 | 名称: E3 ubiquitin-protein ligase RBX1, N-terminally processed タイプ: protein_or_peptide / ID: 6 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 12.289977 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MAAAMDVDTP SGTNSGAGKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM DLCIECQANQ ASATSEECTV AWGVCNHAFH FHCISRWLK TRQVCPLDNR EWEFQKYGH UniProtKB: E3 ubiquitin-protein ligase RBX1 |
-分子 #7: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 7 / コピー数: 8 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: OTHER / 詳細: Model from alphafold |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.54 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 135810 |