登録情報 データベース : EMDB / ID : EMD-44441 ダウンロードとリンクタイトル Cryo-EM structure of the S. cerevisiae ORC-Cdc6-Mcm2-7-DNA complex with a fully closed Mcm2-Mcm5 DNA entry gate マップデータstructure of the S. cerevisiae ORC-Cdc6-Mcm2-7-DNA complex with a fully closed Mcm2-Mcm5 DNA entry gate 詳細 試料複合体 : ORC-Cdc6-Mcm2-7-dsDNAタンパク質・ペプチド : x 14種DNA : x 2種リガンド : x 2種 詳細 キーワード DNA replication / Cryo-EM / OCCM-deltaC6 / REPLICATION-DNA complex / DNA BINDING PROTEIN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
MCM complex loading / : / CDC6 association with the ORC:origin complex / Cul8-RING ubiquitin ligase complex / maintenance of rDNA / MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / MCM complex binding / nuclear DNA replication ... MCM complex loading / : / CDC6 association with the ORC:origin complex / Cul8-RING ubiquitin ligase complex / maintenance of rDNA / MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / MCM complex binding / nuclear DNA replication / Assembly of the ORC complex at the origin of replication / premeiotic DNA replication / nuclear origin of replication recognition complex / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / mitotic DNA replication / Activation of the pre-replicative complex / CMG complex / nuclear pre-replicative complex / nucleosome organization / cyclin-dependent protein serine/threonine kinase inhibitor activity / Activation of ATR in response to replication stress / DNA replication preinitiation complex / MCM complex / replication fork protection complex / mitotic DNA replication checkpoint signaling / double-strand break repair via break-induced replication / single-stranded DNA helicase activity / mitotic DNA replication initiation / regulation of DNA-templated DNA replication initiation / silent mating-type cassette heterochromatin formation / 3'-5' DNA helicase activity / CDK-mediated phosphorylation and removal of Cdc6 / DNA strand elongation involved in DNA replication / Orc1 removal from chromatin / nuclear replication fork / regulation of DNA replication / DNA replication origin binding / DNA replication initiation / subtelomeric heterochromatin formation / nucleosome binding / G1/S transition of mitotic cell cycle / single-stranded DNA binding / chromosome / DNA helicase / forked DNA-dependent helicase activity / single-stranded 3'-5' DNA helicase activity / four-way junction helicase activity / double-stranded DNA helicase activity / chromosome, telomeric region / DNA replication / hydrolase activity / cell division / GTPase activity / DNA damage response / chromatin binding / GTP binding / ATP hydrolysis activity / zinc ion binding / nucleoplasm / ATP binding / metal ion binding / nucleus / cytoplasm 類似検索 - 分子機能 Origin recognition complex, subunit 6, fungi / Cell division protein Cdc6/18 / : / Cdc6/ORC-like, ATPase lid domain / : / Origin recognition complex subunit 1 C-terminal winged HTH domain / Origin recognition complex, subunit 6 / Origin recognition complex subunit 6 (ORC6) / Cdc6, C-terminal / CDC6, C terminal winged helix domain ... Origin recognition complex, subunit 6, fungi / Cell division protein Cdc6/18 / : / Cdc6/ORC-like, ATPase lid domain / : / Origin recognition complex subunit 1 C-terminal winged HTH domain / Origin recognition complex, subunit 6 / Origin recognition complex subunit 6 (ORC6) / Cdc6, C-terminal / CDC6, C terminal winged helix domain / : / AAA domain / Origin recognition complex subunit 4 / Origin recognition complex, subunit 3 / Origin recognition complex, subunit 5 / Origin recognition complex subunit 4, C-terminal / Origin recognition complex subunit 3, winged helix C-terminal / Origin recognition complex subunit 3, N-terminal / : / : / Origin recognition complex (ORC) subunit 3 N-terminus / Origin recognition complex (ORC) subunit 4 C-terminus / Origin recognition complex (ORC) subunit 5 C-terminus / Origin recognition complex winged helix C-terminal / ORC5, lid domain / Orc1-like, AAA ATPase domain / Origin recognition complex subunit 2 RecA-like domain / AAA ATPase domain / Origin recognition complex, subunit 2 / AAA lid domain / AAA lid domain / : / DNA replication licensing factor Mcm5 / DNA replication licensing factor Mcm6 / DNA replication licensing factor Mcm7 / Mcm6, C-terminal winged-helix domain / MCM6 C-terminal winged-helix domain / DNA replication licensing factor Mcm2 / Mini-chromosome maintenance protein 2 / Mini-chromosome maintenance, conserved site / MCM family signature. / Bromo adjacent homology domain / BAH domain / Bromo adjacent homology (BAH) domain / Bromo adjacent homology (BAH) domain superfamily / BAH domain profile. / MCM N-terminal domain / MCM N-terminal domain / MCM OB domain / MCM OB domain / Mini-chromosome maintenance protein / MCM, AAA-lid domain / MCM P-loop domain / MCM AAA-lid domain / MCM family domain profile. / minichromosome maintenance proteins / MCM domain / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / EF-Hand 1, calcium-binding site / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 DNA replication licensing factor MCM5 / : / : / : / Cell division control protein 6 / DNA replication licensing factor MCM2 / Origin recognition complex subunit 2 / DNA replication licensing factor MCM7 / Origin recognition complex subunit 6 / Origin recognition complex subunit 5 ... DNA replication licensing factor MCM5 / : / : / : / Cell division control protein 6 / DNA replication licensing factor MCM2 / Origin recognition complex subunit 2 / DNA replication licensing factor MCM7 / Origin recognition complex subunit 6 / Origin recognition complex subunit 5 / DNA replication licensing factor MCM6 / Origin recognition complex subunit 1 / Origin recognition complex subunit 3 / Origin recognition complex subunit 4 類似検索 - 構成要素生物種 Saccharomyces cerevisiae (パン酵母) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 6.1 Å 詳細 データ登録者Yuan Z / Bai L / Li H / Speck C 資金援助 米国, 英国, 5件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM110387 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM131754 米国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/S001387/1 英国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/N000323/1 英国 Wellcome Trust 107903/Z/15/Z 英国
引用ジャーナル : Nat Commun / 年 : 2025タイトル : MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.著者 : Sarah V Faull / Marta Barbon / Audrey Mossler / Zuanning Yuan / Lin Bai / L Maximilian Reuter / Alberto Riera / Christian Winkler / Indiana Magdalou / Matthew Peach / Huilin Li / Christian Speck / 要旨 : The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP ... The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase. 履歴 登録 2024年4月10日 - ヘッダ(付随情報) 公開 2025年1月1日 - マップ公開 2025年1月1日 - 更新 2025年1月15日 - 現状 2025年1月15日 処理サイト : RCSB / 状態 : 公開
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