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基本情報
登録情報 | データベース: EMDB / ID: EMD-30464 | |||||||||
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タイトル | Human Origin Recognition Complex, ORC1-5 State I | |||||||||
![]() | HsORC1-5-StateI | |||||||||
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![]() | DNA replication initiation / Origin Recognition Complex / cryo-EM / autoinhibition conformation / REPLICATION | |||||||||
機能・相同性 | ![]() polar body extrusion after meiotic divisions / CDC6 association with the ORC:origin complex / origin recognition complex / E2F-enabled inhibition of pre-replication complex formation / nuclear origin of replication recognition complex / nuclear pre-replicative complex / inner kinetochore / DNA replication preinitiation complex / mitotic DNA replication checkpoint signaling / neural precursor cell proliferation ...polar body extrusion after meiotic divisions / CDC6 association with the ORC:origin complex / origin recognition complex / E2F-enabled inhibition of pre-replication complex formation / nuclear origin of replication recognition complex / nuclear pre-replicative complex / inner kinetochore / DNA replication preinitiation complex / mitotic DNA replication checkpoint signaling / neural precursor cell proliferation / G1/S-Specific Transcription / regulation of DNA replication / DNA replication origin binding / protein polymerization / Activation of the pre-replicative complex / DNA replication initiation / glial cell proliferation / heterochromatin / Activation of ATR in response to replication stress / Assembly of the ORC complex at the origin of replication / Assembly of the pre-replicative complex / Orc1 removal from chromatin / DNA replication / chromosome, telomeric region / nuclear body / nucleotide binding / centrosome / chromatin binding / chromatin / nucleolus / negative regulation of transcription by RNA polymerase II / ATP hydrolysis activity / DNA binding / nucleoplasm / ATP binding / membrane / nucleus / metal ion binding / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 5.0 Å | |||||||||
![]() | Cheng J / Li N | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insight into the assembly and conformational activation of human origin recognition complex. 著者: Jiaxuan Cheng / Ningning Li / Xiaohan Wang / Jiazhi Hu / Yuanliang Zhai / Ning Gao / ![]() 要旨: The function of the origin recognition complex (ORC) in DNA replication is highly conserved in recognizing and marking the initiation sites. The detailed molecular mechanisms by which human ORC is ...The function of the origin recognition complex (ORC) in DNA replication is highly conserved in recognizing and marking the initiation sites. The detailed molecular mechanisms by which human ORC is reconfigured into a state competent for origin association remain largely unknown. Here, we present structural characterizations of human ORC1-5 and ORC2-5 assemblies. ORC2-5 exhibits a tightly autoinhibited conformation with the winged-helix domain of ORC2 completely blocking the central DNA-binding channel. The binding of ORC1 partially relieves the autoinhibitory effect of ORC2-5 through remodeling ORC2-WHD, which makes ORC2-WHD away from the central channel creating a still autoinhibited but more dynamic structure. In particular, the AAA+ domain of ORC1 is highly flexible to sample a variety of conformations from inactive to potentially active states. These results provide insights into the detailed mechanisms regulating the autoinhibition of human ORC and its subsequent activation for DNA binding. | |||||||||
履歴 |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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ヘッダ (付随情報) | ![]() ![]() | 17 KB 17 KB | 表示 表示 | ![]() |
画像 | ![]() | 124.2 KB | ||
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | HsORC1-5-StateI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.6572 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : Human Origin Recognition Complex 1-5 State I
全体 | 名称: Human Origin Recognition Complex 1-5 State I |
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要素 |
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-超分子 #1: Human Origin Recognition Complex 1-5 State I
超分子 | 名称: Human Origin Recognition Complex 1-5 State I / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Origin recognition complex subunit 1
分子 | 名称: Origin recognition complex subunit 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 97.499867 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MAHYPTRLKT RKTYSWVGRP LLDRKLHYQT YREMCVKTEG CSTEIHIQIG QFVLIEGDDD ENPYVAKLLE LFEDDSDPPP KKRARVQWF VRFCEVPACK RHLLGRKPGA QEIFWYDYPA CDSNINAETI IGLVRVIPLA PKDVVPTNLK NEKTLFVKLS W NEKKFRPL ...文字列: MAHYPTRLKT RKTYSWVGRP LLDRKLHYQT YREMCVKTEG CSTEIHIQIG QFVLIEGDDD ENPYVAKLLE LFEDDSDPPP KKRARVQWF VRFCEVPACK RHLLGRKPGA QEIFWYDYPA CDSNINAETI IGLVRVIPLA PKDVVPTNLK NEKTLFVKLS W NEKKFRPL SSELFAELNK PQESAAKCQK PVRAKSKSAE SPSWTPAEHV AKRIESRHSA SKSRQTPTHP LTPRARKRLE LG NLGNPQM SQQTSCASLD SPGRIKRKVA FSEITSPSKR SQPDKLQTLS PALKAPEKTR ETGLSYTEDD KKASPEHRII LRT RIAASK TIDIREERTL TPISGGQRSS VVPSVILKPE NIKKRDAKEA KAQNEATSTP HRIRRKSSVL TMNRIRQQLR FLGN SKSDQ EEKEILPAAE ISDSSSDEEE ASTPPLPRRA PRTVSRNLRS SLKSSLHTLT KVPKKSLKPR TPRCAAPQIR SRSLA AQEP ASVLEEARLR LHVSAVPESL PCREQEFQDI YNFVESKLLD HTGGCMYISG VPGTGKTATV HEVIRCLQQA AQANDV PPF QYIEVNGMKL TEPHQVYVQI LQKLTGQKAT ANHAAELLAK QFCTRGSPQE TTVLLVDELD LLWTHKQDIM YNLFDWP TH KEARLVVLAI ANTMDLPERI MMNRVSSRLG LTRMCFQPYT YSQLQQILRS RLKHLKAFED DAIQLVARKV AALSGDAR R CLDICRRATE ICEFSQQKPD SPGLVTIAHS MEAVDEMFSS SYITAIKNSS VLEQSFLRAI LAEFRRSGLE EATFQQIYS QHVALCRMEG LPYPTMSETM AVCSHLGSCR LLLVEPSRND LLLRVRLNVS QDDVLYALKD E UniProtKB: Origin recognition complex subunit 1 |
-分子 #2: Origin recognition complex subunit 2
分子 | 名称: Origin recognition complex subunit 2 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 66.063375 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSKPELKEDK MLEVHFVGDD DVLNHILDRE GGAKLKKERA QLLVNPKKII KKPEYDLEED DQEVLKDQNY VEIMGRDVQE SLKNGSATG GGNKVYSFQN RKHSEKMAKL ASELAKTPQK SVSFSLKNDP EITINVPQSS KGHSASDKVQ PKNNDKSEFL S TAPRSLRK ...文字列: MSKPELKEDK MLEVHFVGDD DVLNHILDRE GGAKLKKERA QLLVNPKKII KKPEYDLEED DQEVLKDQNY VEIMGRDVQE SLKNGSATG GGNKVYSFQN RKHSEKMAKL ASELAKTPQK SVSFSLKNDP EITINVPQSS KGHSASDKVQ PKNNDKSEFL S TAPRSLRK RLIVPRSHSD SESEYSASNS EDDEGVAQEH EEDTNAVIFS QKIQAQNRVV SAPVGKETPS KRMKRDKTSD LV EEYFEAH SSSKVLTSDR TLQKLKRAKL DQQTLRNLLS KVSPSFSAEL KQLNQQYEKL FHKWMLQLHL GFNIVLYGLG SKR DLLERF RTTMLQDSIH VVINGFFPGI SVKSVLNSIT EEVLDHMGTF RSILDQLDWI VNKFKEDSSL ELFLLIHNLD SQML RGEKS QQIIGQLSSL HNIYLIASID HLNAPLMWDH AKQSLFNWLW YETTTYSPYT EETSYENSLL VKQSGSLPLS SLTHV LRSL TPNARGIFRL LIKYQLDNQD NPSYIGLSFQ DFYQQCREAF LVNSDLTLRA QLTEFRDHKL IRTKKGTDGV EYLLIP VDN GTLTDFLEKE EEEA UniProtKB: Origin recognition complex subunit 2 |
-分子 #3: Origin recognition complex subunit 3
分子 | 名称: Origin recognition complex subunit 3 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 82.365055 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MATSSMSKGC FVFKPNSKKR KISLPIEDYF NKGKNEPEDS KLRFETYQLI WQQMKSENER LQEELNKNLF DNLIEFLQKS HSGFQKNSR DLGGQIKLRE IPTAALVLGV NVTDHDLTFG SLTEALQNNV TPYVVSLQAK DCPDMKHFLQ KLISQLMDCC V DIKSKEEE ...文字列: MATSSMSKGC FVFKPNSKKR KISLPIEDYF NKGKNEPEDS KLRFETYQLI WQQMKSENER LQEELNKNLF DNLIEFLQKS HSGFQKNSR DLGGQIKLRE IPTAALVLGV NVTDHDLTFG SLTEALQNNV TPYVVSLQAK DCPDMKHFLQ KLISQLMDCC V DIKSKEEE SVHVTQRKTH YSMDSLSSWY MTVTQKTDPK MLSKKRTTSS QWQSPPVVVI LKDMESFATK VLQDFIIISS QH LHEFPLI LIFGIATSPI IIHRLLPHAV SSLLCIELFQ SLSCKEHLTT VLDKLLLTTQ FPFKINEKVL QVLTNIFLYH DFS VQNFIK GLQLSLLEHF YSQPLSVLCC NLPEAKRRIN FLSNNQCENI RRLPSFRRYV EKQASEKQVA LLTNERYLKE ETQL LLENL HVYHMNYFLV LRCLHKFTSS LPKYPLGRQI RELYCTCLEK NIWDSEEYAS VLQLLRMLAK DELMTILEKC FKVFK SYCE NHLGSTAKRI EEFLAQFQSL DETKEEEDAS GSQPKGLQKT DLYHLQKSLL EMKELRRSKK QTKFEVLREN VVNFID CLV REYLLPPETQ PLHEVVYFSA AHALREHLNA APRIALHTAL NNPYYYLKNE ALKSEEGCIP NIAPDICIAY KLHLECS RL INLVDWSEAF ATVVTAAEKM DANSATSEEM NEIIHARFIR AVSELELLGF IKPTKQKTDH VARLTWGGC UniProtKB: Origin recognition complex subunit 3 |
-分子 #4: Origin recognition complex subunit 4
分子 | 名称: Origin recognition complex subunit 4 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 50.44425 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES NSVLIIGPRG SGKTMLINHA LKELMEIEE VSENVLQVHL NGLLQINDKI ALKEITRQLN LENVVGDKVF GSFAENLSFL LEALKKGDRT SSCPVIFILD E FDLFAHHK ...文字列: MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES NSVLIIGPRG SGKTMLINHA LKELMEIEE VSENVLQVHL NGLLQINDKI ALKEITRQLN LENVVGDKVF GSFAENLSFL LEALKKGDRT SSCPVIFILD E FDLFAHHK NQTLLYNLFD ISQSAQTPIA VIGLTCRLDI LELLEKRVKS RFSHRQIHLM NSFGFPQYVK IFKEQLSLPA EF PDKVFAE KWNENVQYLS EDRSVQEVLQ KHFNISKNLR SLHMLLMLAL NRVTASHPFM TAVDLMEASQ LCSMDSKANI VHG LSVLEI CLIIAMKHLN DIYEEEPFNF QMVYNEFQKF VQRKAHSVYN FEKPVVMKAF EHLQQLELIK PMERTSGNSE REYQ LMKLL LDNTQIMNAL QKYPNCPTDV RQWATSSLSW L UniProtKB: Origin recognition complex subunit 4 |
-分子 #5: Origin recognition complex subunit 5
分子 | 名称: Origin recognition complex subunit 5 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 50.349934 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MPHLENVVLC RESQVSILQS LFGERHHFSF PSIFIYGHTA SGKTYVTQTL LKTLELPHVF VNCVECFTLR LLLEQILNKL NHLSSSEDG CSTEITCETF NDFVRLFKQV TTAENLKDQT VYIVLDKAEY LRDMEANLLP GFLRLQELAD RNVTVLFLSE I VWEKFRPN ...文字列: MPHLENVVLC RESQVSILQS LFGERHHFSF PSIFIYGHTA SGKTYVTQTL LKTLELPHVF VNCVECFTLR LLLEQILNKL NHLSSSEDG CSTEITCETF NDFVRLFKQV TTAENLKDQT VYIVLDKAEY LRDMEANLLP GFLRLQELAD RNVTVLFLSE I VWEKFRPN TGCFEPFVLY FPDYSIGNLQ KILSHDHPPE YSADFYAAYI NILLGVFYTV CRDLKELRHL AVLNFPKYCE PV VKGEASE RDTRKLWRNI EPHLKKAMQT VYLREISSSQ WEKLQKDDTD PGQLKGLSAH THVELPYYSK FILIAAYLAS YNP ARTDKR FFLKHHGKIK KTNFLKKHEK TSNHLLGPKP FPLDRLLAIL YSIVDSRVAP TANIFSQITS LVTLQLLTLV GHDD QLDGP KYKCTVSLDF IRAIARTVNF DIIKYLYDFL UniProtKB: Origin recognition complex subunit 5 |
-分子 #6: ADENOSINE-5'-TRIPHOSPHATE
分子 | 名称: ADENOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 6 / コピー数: 2 / 式: ATP |
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分子量 | 理論値: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.6 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 65.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: PDB ENTRY |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 5.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 49000 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |