+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 5l9u | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Model of human Anaphase-promoting complex/Cyclosome (APC/C-CDH1) with a cross linked Ubiquitin variant-substrate-UBE2C (UBCH10) complex representing key features of multiubiquitination | ||||||||||||||||||
![]() |
| ||||||||||||||||||
![]() | SIGNALING PROTEIN / ubiquitination / multi-protein complex / cell division | ||||||||||||||||||
機能・相同性 | ![]() : / : / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Activated NOTCH1 Transmits Signal to the Nucleus / Downregulation of TGF-beta receptor signaling / Regulation of FZD by ubiquitination / Regulation of TNFR1 signaling ...: / : / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Activated NOTCH1 Transmits Signal to the Nucleus / Downregulation of TGF-beta receptor signaling / Regulation of FZD by ubiquitination / Regulation of TNFR1 signaling / TNFR1-induced NF-kappa-B signaling pathway / Translesion synthesis by POLK / Translesion synthesis by POLI / Termination of translesion DNA synthesis / Gap-filling DNA repair synthesis and ligation in GG-NER / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Fanconi Anemia Pathway / Regulation of TP53 Degradation / Regulation of TP53 Activity through Methylation / Cyclin D associated events in G1 / Stabilization of p53 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / ER Quality Control Compartment (ERQC) / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Alpha-protein kinase 1 signaling pathway / Inactivation of CSF3 (G-CSF) signaling / : / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOD1/2 Signaling Pathway / activated TAK1 mediates p38 MAPK activation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Dual Incision in GG-NER / E3 ubiquitin ligases ubiquitinate target proteins / Translesion Synthesis by POLH / Downregulation of ERBB2:ERBB3 signaling / TCF dependent signaling in response to WNT / Regulation of innate immune responses to cytosolic DNA / HDR through Homologous Recombination (HRR) / Downregulation of ERBB2 signaling / Regulation of signaling by CBL / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / NOTCH3 Activation and Transmission of Signal to the Nucleus / protein localization to septin ring / Downregulation of ERBB4 signaling / Stimuli-sensing channels / Deactivation of the beta-catenin transactivating complex / Josephin domain DUBs / Ovarian tumor domain proteases / Negative regulation of MET activity / Interleukin-1 signaling / Regulation of PTEN localization / mitotic morphogenesis checkpoint signaling / Pexophagy / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Metalloprotease DUBs / Regulation of necroptotic cell death / Aggrephagy / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / NRIF signals cell death from the nucleus / NF-kB is activated and signals survival / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / UCH proteinases / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / The role of GTSE1 in G2/M progression after G2 checkpoint / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX3 expression and activity / p75NTR recruits signalling complexes / GLI3 is processed to GLI3R by the proteasome / Activation of NF-kappaB in B cells / Degradation of beta-catenin by the destruction complex / Degradation of AXIN / Regulation of RAS by GAPs / Orc1 removal from chromatin / Neddylation / EGFR downregulation 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: 6.4 Å | ||||||||||||||||||
![]() | Brown, N.G. / VanderLinden, R. / Dube, P. / Haselbach, D. / Peters, J.M. / Stark, H. / Schulman, B.A. | ||||||||||||||||||
資金援助 | ![]() ![]()
| ||||||||||||||||||
![]() | ![]() タイトル: Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. 著者: Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / ...著者: Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / Renping Qiao / Ying Lu / Prakash Dube / Michael R Brunner / Christy R R Grace / Darcie J Miller / David Haselbach / Marc A Jarvis / Masaya Yamaguchi / David Yanishevski / Georg Petzold / Sachdev S Sidhu / Brian Kuhlman / Marc W Kirschner / J Wade Harper / Jan-Michael Peters / Holger Stark / Brenda A Schulman / ![]() ![]() ![]() ![]() 要旨: Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of ...Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination. | ||||||||||||||||||
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 | ![]() | 366.4 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 203.5 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 | ![]() | 961.6 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 961.9 KB | 表示 | |
XML形式データ | ![]() | 88.5 KB | 表示 | |
CIF形式データ | ![]() | 136.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
-Anaphase-promoting complex subunit ... , 11種, 13分子 ABDEGWILMNOXY
#1: タンパク質 | 分子量: 216725.469 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
#2: タンパク質 | 分子量: 9854.647 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() | ||||||||||||
#4: タンパク質 | 分子量: 14286.727 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() | ||||||||||||
#5: タンパク質 | 分子量: 11677.995 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() | ||||||||||||
#7: タンパク質 | 分子量: 9793.999 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #8: タンパク質 | | 分子量: 93207.328 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: Construct contains the remnant of PreScission Protease site at C-terminus. 由来: (組換発現) ![]() ![]() #10: タンパク質 | | 分子量: 21282.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #11: タンパク質 | | 分子量: 8528.309 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #12: タンパク質 | | 分子量: 93938.977 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #13: タンパク質 | | 分子量: 85179.766 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #17: タンパク質 | 分子量: 63204.020 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-Cell division cycle protein ... , 3種, 6分子 CPFHJK
#3: タンパク質 | 分子量: 68921.031 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #6: タンパク質 | 分子量: 91973.125 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #9: タンパク質 | 分子量: 71747.516 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
---|
-タンパク質 , 3種, 3分子 RSU
#14: タンパク質 | 分子量: 54838.688 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
---|---|
#15: タンパク質 | 分子量: 17057.281 Da / 分子数: 1 / Mutation: K788C,K788C,K788C / 由来タイプ: 組換発現 詳細: This construct comprises 768-842 of HSL1 with an N-terminal Gemini-IM motif and linker and a C-terminal UB variant (CHAIN V). K788C of this construct is cross-linked to UBE2C C115 (CHAIN U) ...詳細: This construct comprises 768-842 of HSL1 with an N-terminal Gemini-IM motif and linker and a C-terminal UB variant (CHAIN V). K788C of this construct is cross-linked to UBE2C C115 (CHAIN U) and to UbG75C (not visible) via TMEA. 由来: (組換発現) ![]() ![]() ![]() ![]() 遺伝子: HSL1, YKL101W, YKL453 / 発現宿主: ![]() ![]() 参照: UniProt: P34244, UniProt: Q63429, non-specific serine/threonine protein kinase |
#16: タンパク質 | 分子量: 20768.289 Da / 分子数: 1 / Mutation: C102A / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: O00762, E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme |
-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 | 名称: Multi-protein complex of APC/C, coactivator CDH1, and cross-linked complex of UBE2C, Ubiquitin, and Substrate-UB_variant fusion. タイプ: COMPLEX / Entity ID: all |
---|---|
分子量 | 値: 1.28 MDa / 実験値: NO |
緩衝液 | pH: 8 |
試料 | 濃度: 0.1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
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 |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
-
解析
EMソフトウェア | 名称: RELION / バージョン: 1.2 / カテゴリ: 3次元再構成 |
---|---|
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 6.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 135578 / 対称性のタイプ: POINT |