登録情報 データベース : EMDB / ID : EMD-12368 構造の表示 ダウンロードとリンクタイトル CryoEM structure of the human Separase-Cdk1-cyclin B1-Cks1 complex マップデータSeparase-Cdk1-cyclin B1-Cks1 complex (postprocessed). 詳細 試料複合体 : Mutual inhibitory complex of human separase-Cdk1-cyclin B1-Cks1 (CCC) complex.タンパク質・ペプチド : Securin,Separinタンパク質・ペプチド : Cyclin-dependent kinase 1タンパク質・ペプチド : G2/mitotic-specific cyclin-B1,G2/mitotic-specific cyclin-B1タンパク質・ペプチド : Cyclin-dependent kinases regulatory subunit 1リガンド : PHOSPHATE ION 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
negative regulation of mitotic sister chromatid separation / negative regulation of sister chromatid cohesion / separase / regulation of Schwann cell differentiation / pronuclear fusion / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / Mitotic Prophase / positive regulation of mitotic sister chromatid segregation / meiotic chromosome separation ... negative regulation of mitotic sister chromatid separation / negative regulation of sister chromatid cohesion / separase / regulation of Schwann cell differentiation / pronuclear fusion / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / Mitotic Prophase / positive regulation of mitotic sister chromatid segregation / meiotic chromosome separation / histone kinase activity / Golgi disassembly / microtubule cytoskeleton organization involved in mitosis / G2/M DNA replication checkpoint / E2F-enabled inhibition of pre-replication complex formation / ventricular cardiac muscle cell development / Depolymerization of the Nuclear Lamina / positive regulation of attachment of spindle microtubules to kinetochore / MASTL Facilitates Mitotic Progression / regulation of mitotic cell cycle spindle assembly checkpoint / establishment of mitotic spindle localization / Activation of NIMA Kinases NEK9, NEK6, NEK7 / homologous chromosome segregation / mitotic nuclear membrane disassembly / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / Phosphorylation of Emi1 / cyclin A2-CDK1 complex / patched binding / meiotic spindle organization / Nuclear Pore Complex (NPC) Disassembly / Transcriptional regulation by RUNX2 / Phosphorylation of the APC/C / outer kinetochore / mitotic cell cycle phase transition / positive regulation of mitotic metaphase/anaphase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Initiation of Nuclear Envelope (NE) Reformation / protein localization to kinetochore / Polo-like kinase mediated events / Golgi Cisternae Pericentriolar Stack Reorganization / cyclin-dependent protein serine/threonine kinase activator activity / Condensation of Prometaphase Chromosomes / response to copper ion / chromosome condensation / centrosome cycle / [RNA-polymerase]-subunit kinase / cyclin-dependent protein serine/threonine kinase regulator activity / SCF ubiquitin ligase complex / cysteine-type endopeptidase inhibitor activity / mitotic metaphase chromosome alignment / G1/S-Specific Transcription / cyclin-dependent protein kinase activity / MAPK3 (ERK1) activation / ubiquitin-like protein ligase binding / response to amine / mitotic sister chromatid segregation / mitotic G2 DNA damage checkpoint signaling / Regulation of APC/C activators between G1/S and early anaphase / regulation of embryonic development / cellular response to organic cyclic compound / mitotic cytokinesis / response to axon injury / chromosome organization / cyclin-dependent kinase / catalytic activity / animal organ regeneration / cyclin-dependent protein serine/threonine kinase activity / Nuclear events stimulated by ALK signaling in cancer / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / cyclin-dependent protein kinase holoenzyme complex / response to cadmium ion / Cyclin A/B1/B2 associated events during G2/M transition / cysteine-type peptidase activity / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / positive regulation of cardiac muscle cell proliferation / Recruitment of mitotic centrosome proteins and complexes / Recruitment of NuMA to mitotic centrosomes / epithelial cell differentiation / Resolution of Sister Chromatid Cohesion / Anchoring of the basal body to the plasma membrane / regulation of mitotic cell cycle / Hsp70 protein binding / positive regulation of G2/M transition of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / ERK1 and ERK2 cascade / positive regulation of mitotic cell cycle / cyclin binding / AURKA Activation by TPX2 / RNA polymerase II CTD heptapeptide repeat kinase activity / Condensation of Prophase Chromosomes / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / mitotic spindle organization / positive regulation of DNA replication / APC/C:Cdc20 mediated degradation of Securin / response to activity / ubiquitin binding / molecular function activator activity / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / spindle microtubule 類似検索 - 分子機能 Securin sister-chromatid separation inhibitor / Securin sister-chromatid separation inhibitor / Peptidase C50, separase / SEPARIN core domain / SEPARIN core domain profile. / : / Cyclin-dependent kinase, regulatory subunit / Cyclin-dependent kinase, regulatory subunit superfamily / Cyclin-dependent kinase regulatory subunit / Cyclin-dependent kinases regulatory subunits signature 1. ... Securin sister-chromatid separation inhibitor / Securin sister-chromatid separation inhibitor / Peptidase C50, separase / SEPARIN core domain / SEPARIN core domain profile. / : / Cyclin-dependent kinase, regulatory subunit / Cyclin-dependent kinase, regulatory subunit superfamily / Cyclin-dependent kinase regulatory subunit / Cyclin-dependent kinases regulatory subunits signature 1. / Cyclin-dependent kinases regulatory subunits signature 2. / Cyclin-dependent kinase regulatory subunit / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Securin / Cyclin-dependent kinase 1 / G2/mitotic-specific cyclin-B1 / Cyclin-dependent kinases regulatory subunit 1 / Separin 類似検索 - 構成要素生物種 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 : 3.6 Å 詳細 データ登録者Yu J / Raia P / Ghent CM / Raisch T / Sadian Y / Barford D / Raunser S / Morgan DO / Boland A 資金援助 スイス, 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 Swiss National Science Foundation 310030_185235 スイス National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R35-GM118053 米国
引用ジャーナル : Nature / 年 : 2021タイトル : Structural basis of human separase regulation by securin and CDK1-cyclin B1.著者 : Jun Yu / Pierre Raia / Chloe M Ghent / Tobias Raisch / Yashar Sadian / Simone Cavadini / Pramod M Sabale / David Barford / Stefan Raunser / David O Morgan / Andreas Boland / 要旨 : In early mitosis, the duplicated chromosomes are held together by the ring-shaped cohesin complex. Separation of chromosomes during anaphase is triggered by separase-a large cysteine endopeptidase ... In early mitosis, the duplicated chromosomes are held together by the ring-shaped cohesin complex. Separation of chromosomes during anaphase is triggered by separase-a large cysteine endopeptidase that cleaves the cohesin subunit SCC1 (also known as RAD21). Separase is activated by degradation of its inhibitors, securin and cyclin B, but the molecular mechanisms of separase regulation are not clear. Here we used cryogenic electron microscopy to determine the structures of human separase in complex with either securin or CDK1-cyclin B1-CKS1. In both complexes, separase is inhibited by pseudosubstrate motifs that block substrate binding at the catalytic site and at nearby docking sites. As in Caenorhabditis elegans and yeast, human securin contains its own pseudosubstrate motifs. By contrast, CDK1-cyclin B1 inhibits separase by deploying pseudosubstrate motifs from intrinsically disordered loops in separase itself. One autoinhibitory loop is oriented by CDK1-cyclin B1 to block the catalytic sites of both separase and CDK1. Another autoinhibitory loop blocks substrate docking in a cleft adjacent to the separase catalytic site. A third separase loop contains a phosphoserine that promotes complex assembly by binding to a conserved phosphate-binding pocket in cyclin B1. Our study reveals the diverse array of mechanisms by which securin and CDK1-cyclin B1 bind and inhibit separase, providing the molecular basis for the robust control of chromosome segregation. 履歴 登録 2021年2月14日 - ヘッダ(付随情報) 公開 2021年8月4日 - マップ公開 2021年8月4日 - 更新 2021年8月18日 - 現状 2021年8月18日 処理サイト : PDBe / 状態 : 公開
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