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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30464 | |||||||||
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Title | 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 | |||||||||
Function / homology | ![]() 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 Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.0 Å | |||||||||
![]() | Cheng J / Li N | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insight into the assembly and conformational activation of human origin recognition complex. Authors: Jiaxuan Cheng / Ningning Li / Xiaohan Wang / Jiazhi Hu / Yuanliang Zhai / Ning Gao / ![]() Abstract: 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. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 1.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17 KB 17 KB | Display Display | ![]() |
Images | ![]() | 124.2 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ctgMC ![]() 7cteC ![]() 7ctfC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | HsORC1-5-StateI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.6572 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Human Origin Recognition Complex 1-5 State I
Entire | Name: Human Origin Recognition Complex 1-5 State I |
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Components |
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-Supramolecule #1: Human Origin Recognition Complex 1-5 State I
Supramolecule | Name: Human Origin Recognition Complex 1-5 State I / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Origin recognition complex subunit 1
Macromolecule | Name: Origin recognition complex subunit 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 97.499867 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAHYPTRLKT RKTYSWVGRP LLDRKLHYQT YREMCVKTEG CSTEIHIQIG QFVLIEGDDD ENPYVAKLLE LFEDDSDPPP KKRARVQWF VRFCEVPACK RHLLGRKPGA QEIFWYDYPA CDSNINAETI IGLVRVIPLA PKDVVPTNLK NEKTLFVKLS W NEKKFRPL ...String: 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 |
-Macromolecule #2: Origin recognition complex subunit 2
Macromolecule | Name: Origin recognition complex subunit 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 66.063375 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSKPELKEDK MLEVHFVGDD DVLNHILDRE GGAKLKKERA QLLVNPKKII KKPEYDLEED DQEVLKDQNY VEIMGRDVQE SLKNGSATG GGNKVYSFQN RKHSEKMAKL ASELAKTPQK SVSFSLKNDP EITINVPQSS KGHSASDKVQ PKNNDKSEFL S TAPRSLRK ...String: 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 |
-Macromolecule #3: Origin recognition complex subunit 3
Macromolecule | Name: Origin recognition complex subunit 3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 82.365055 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MATSSMSKGC FVFKPNSKKR KISLPIEDYF NKGKNEPEDS KLRFETYQLI WQQMKSENER LQEELNKNLF DNLIEFLQKS HSGFQKNSR DLGGQIKLRE IPTAALVLGV NVTDHDLTFG SLTEALQNNV TPYVVSLQAK DCPDMKHFLQ KLISQLMDCC V DIKSKEEE ...String: 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 |
-Macromolecule #4: Origin recognition complex subunit 4
Macromolecule | Name: Origin recognition complex subunit 4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 50.44425 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES NSVLIIGPRG SGKTMLINHA LKELMEIEE VSENVLQVHL NGLLQINDKI ALKEITRQLN LENVVGDKVF GSFAENLSFL LEALKKGDRT SSCPVIFILD E FDLFAHHK ...String: 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 |
-Macromolecule #5: Origin recognition complex subunit 5
Macromolecule | Name: Origin recognition complex subunit 5 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 50.349934 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MPHLENVVLC RESQVSILQS LFGERHHFSF PSIFIYGHTA SGKTYVTQTL LKTLELPHVF VNCVECFTLR LLLEQILNKL NHLSSSEDG CSTEITCETF NDFVRLFKQV TTAENLKDQT VYIVLDKAEY LRDMEANLLP GFLRLQELAD RNVTVLFLSE I VWEKFRPN ...String: 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 |
-Macromolecule #6: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 6 / Number of copies: 2 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.6 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 65.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 5.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 49000 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |