+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-3672 | |||||||||
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Title | Open protomer of human ATM (Ataxia telangiectasia mutated) | |||||||||
Map data | Open protomer of human ATM (Ataxia telangiectasia mutated) | |||||||||
Sample |
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Keywords | FAT / MRN / DNA-repair / HEAT-repeats / Transferase | |||||||||
Function / homology | Function and homology information positive regulation of DNA catabolic process / establishment of RNA localization to telomere / positive regulation of telomerase catalytic core complex assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / cellular response to nitrosative stress / establishment of protein-containing complex localization to telomere / negative regulation of telomere capping / Sensing of DNA Double Strand Breaks / positive regulation of telomere maintenance via telomere lengthening / regulation of microglial cell activation ...positive regulation of DNA catabolic process / establishment of RNA localization to telomere / positive regulation of telomerase catalytic core complex assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / cellular response to nitrosative stress / establishment of protein-containing complex localization to telomere / negative regulation of telomere capping / Sensing of DNA Double Strand Breaks / positive regulation of telomere maintenance via telomere lengthening / regulation of microglial cell activation / meiotic telomere clustering / pre-B cell allelic exclusion / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / male meiotic nuclear division / histone mRNA catabolic process / female meiotic nuclear division / pexophagy / cellular response to X-ray / regulation of telomere maintenance via telomerase / peptidyl-serine autophosphorylation / DNA double-strand break processing / lipoprotein catabolic process / V(D)J recombination / regulation of autophagosome assembly / oocyte development / Impaired BRCA2 binding to PALB2 / reciprocal meiotic recombination / DNA repair complex / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / 1-phosphatidylinositol-3-kinase activity / response to ionizing radiation / mitotic spindle assembly checkpoint signaling / TP53 Regulates Transcription of Caspase Activators and Caspases / negative regulation of B cell proliferation / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / peroxisomal matrix / positive regulation of cell adhesion / replicative senescence / Regulation of HSF1-mediated heat shock response / signal transduction in response to DNA damage / somitogenesis / regulation of cellular response to heat / cellular response to retinoic acid / ovarian follicle development / negative regulation of TORC1 signaling / positive regulation of telomere maintenance via telomerase / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / Pexophagy / telomere maintenance / post-embryonic development / thymus development / Meiotic recombination / DNA Damage/Telomere Stress Induced Senescence / regulation of signal transduction by p53 class mediator / DNA damage checkpoint signaling / regulation of autophagy / Nonhomologous End-Joining (NHEJ) / determination of adult lifespan / TP53 Regulates Transcription of DNA Repair Genes / Stabilization of p53 / Autodegradation of the E3 ubiquitin ligase COP1 / G2/M DNA damage checkpoint / double-strand break repair via homologous recombination / cellular response to reactive oxygen species / brain development / multicellular organism growth / HDR through Homologous Recombination (HRR) / Regulation of TP53 Activity through Methylation / cellular senescence / cellular response to gamma radiation / spindle / double-strand break repair via nonhomologous end joining / Regulation of TP53 Degradation / intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of neuron apoptotic process / double-strand break repair / Processing of DNA double-strand break ends / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / heart development / peptidyl-serine phosphorylation / site of double-strand break / cytoplasmic vesicle / Regulation of TP53 Activity through Phosphorylation / neuron apoptotic process / regulation of apoptotic process / protein autophosphorylation / response to hypoxia / regulation of cell cycle / non-specific serine/threonine protein kinase / positive regulation of cell migration Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.7 Å | |||||||||
Authors | Baretic D / Pollard HK | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Sci Adv / Year: 2017 Title: Structures of closed and open conformations of dimeric human ATM. Authors: Domagoj Baretić / Hannah K Pollard / David I Fisher / Christopher M Johnson / Balaji Santhanam / Caroline M Truman / Tomas Kouba / Alan R Fersht / Christopher Phillips / Roger L Williams / Abstract: ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase-related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, ...ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase-related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate-binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_3672.map.gz | 94.3 MB | EMDB map data format | |
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Header (meta data) | emd-3672-v30.xml emd-3672.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_3672_fsc.xml | 10.5 KB | Display | FSC data file |
Images | emd_3672.png | 141.3 KB | ||
Filedesc metadata | emd-3672.cif.gz | 8.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-3672 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3672 | HTTPS FTP |
-Validation report
Summary document | emd_3672_validation.pdf.gz | 280.9 KB | Display | EMDB validaton report |
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Full document | emd_3672_full_validation.pdf.gz | 280 KB | Display | |
Data in XML | emd_3672_validation.xml.gz | 11.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3672 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3672 | HTTPS FTP |
-Related structure data
Related structure data | 5np1MC 3668C 3669C 3670C 3671C 3673C 5np0C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_3672.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Open protomer of human ATM (Ataxia telangiectasia mutated) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.43 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Dimeric human ATM (Ataxia telangiectasia mutated) kinase
Entire | Name: Dimeric human ATM (Ataxia telangiectasia mutated) kinase |
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Components |
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-Supramolecule #1: Dimeric human ATM (Ataxia telangiectasia mutated) kinase
Supramolecule | Name: Dimeric human ATM (Ataxia telangiectasia mutated) kinase type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 705 KDa |
-Macromolecule #1: Serine-protein kinase ATM
Macromolecule | Name: Serine-protein kinase ATM / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 352.393969 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDYKDDDDKH MSLVLNDLLI CCRQLEHDRA TERKKEVEKF KRLIRDPETI KHLDRHSDSK QGKYLNWDAV FRFLQKYIQK ETECLRIAK PNVSASTQAS RQKKMQEISS LVKYFIKCAN RRAPRLKCQE LLNYIMDTVK DSSNGAIYGA DCSNILLKDI L SVRKYWCE ...String: MDYKDDDDKH MSLVLNDLLI CCRQLEHDRA TERKKEVEKF KRLIRDPETI KHLDRHSDSK QGKYLNWDAV FRFLQKYIQK ETECLRIAK PNVSASTQAS RQKKMQEISS LVKYFIKCAN RRAPRLKCQE LLNYIMDTVK DSSNGAIYGA DCSNILLKDI L SVRKYWCE ISQQQWLELF SVYFRLYLKP SQDVHRVLVA RIIHAVTKGC CSQTDGLNSK FLDFFSKAIQ CARQEKSSSG LN HILAALT IFLKTLAVNF RIRVCELGDE ILPTLLYIWT QHRLNDSLKE VIIELFQLQI YIHHPKGAKT QEKGAYESTK WRS ILYNLY DLLVNEISHI GSRGKYSSGF RNIAVKENLI ELMADICHQV FNEDTRSLEI SQSYTTTQRE SSDYSVPCKR KKIE LGWEV IKDHLQKSQN DFDLVPWLQI ATQLISKYPA SLPNCELSPL LMILSQLLPQ QRHGERTPYV LRCLTEVALC QDKRS NLES SQKSDLLKLW NKIWCITFRG ISSEQIQAEN FGLLGAIIQG SLVEVDREFW KLFTGSACRP SCPAVCCLTL ALTTSI VPG TVKMGIEQNM CEVNRSFSLK ESIMKWLLFY QLEGDLENST EVPPILHSNF PHLVLEKILV SLTMKNCKAA MNFFQSV PE CEHHQKDKEE LSFSEVEELF LQTTFDKMDF LTIVRECGIE KHQSSIGFSV HQNLKESLDR CLLGLSEQLL NNYSSEIT N SETLVRCSRL LVGVLGCYCY MGVIAEEEAY KSELFQKAKS LMQCAGESIT LFKNKTNEEF RIGSLRNMMQ LCTRCLSNC TKKSPNKIAS GFFLRLLTSK LMNDIADICK SLASFIKKPF DRGEVESMED DTNGNLMEVE DQSSMNLFND YPDSSVSDAN EPGESQSTI GAINPLAEEY LSKQDLLFLD MLKFLCLCVT TAQTNTVSFR AADIRRKLLM LIDSSTLEPT KSLHLHMYLM L LKELPGEE YPLPMEDVLE LLKPLSNVCS LYRRDQDVCK TILNHVLHVV KNLGQSNMDS ENTRDAQGQF LTVIGAFWHL TK ERKYIFS VRMALVNCLK TLLEADPYSK WAILNVMGKD FPVNEVFTQF LADNHHQVRM LAAESINRLF QDTKGDSSRL LKA LPLKLQ QTAFENAYLK AQEGMREMSH SAENPETLDE IYNRKSVLLT LIAVVLSCSP ICEKQALFAL CKSVKENGLE PHLV KKVLE KVSETFGYRR LEDFMASHLD YLVLEWLNLQ DTEYNLSSFP FILLNYTNIE DFYRSCYKVL IPHLVIRSHF DEVKS IANQ IQEDWKSLLT DCFPKILVNI LPYFAYEGTR DSGMAQQRET ATKVYDMLKS ENLLGKQIDH LFISNLPEIV VELLMT LHE PANSSASQST DLCDFSGDLD PAPNPPHFPS HVIKATFAYI SNCHKTKLKS ILEILSKSPD SYQKILLAIC EQAAETN NV YKKHRILKIY HLFVSLLLKD IKSGLGGAWA FVLRDVIYTL IHYINQRPSC IMDVSLRSFS LCCDLLSQVC QTAVTYCK D ALENHLHVIV GTLIPLVYEQ VEVQKQVLDL LKYLVIDNKD NENLYITIKL LDPFPDHVVF KDLRITQQKI KYSRGPFSL LEEINHFLSV SVYDALPLTR LEGLKDLRRQ LELHKDQMVD IMRASQDNPQ DGIMVKLVVN LLQLSKMAIN HTGEKEVLEA VGSCLGEVG PIDFSTIAIQ HSKDASYTKA LKLFEDKELQ WTFIMLTYLN NTLVEDCVKV RSAAVTCLKN ILATKTGHSF W EIYKMTTD PMLAYLQPFR TSRKKFLEVP RFDKENPFEG LDDINLWIPL SENHDIWIKT LTCAFLDSGG TKCEILQLLK PM CEVKTDF CQTVLPYLIH DILLQDTNES WRNLLSTHVQ GFFTSCLRHF SQTSRSTTPA NLDSESEHFF RCCLDKKSQR TML AVVDYM RRQKRPSSGT IFNDAFWLDL NYLEVAKVAQ SCAAHFTALL YAEIYADKKS MDDQEKRSLA FEEGSQSTTI SSLS EKSKE ETGISLQDLL LEIYRSIGEP DSLYGCGGGK MLQPITRLRT YEHEAMWGKA LVTYDLETAI PSSTRQAGII QALQN LGLC HILSVYLKGL DYENKDWCPE LEELHYQAAW RNMQWDHCTS VSKEVEGTSY HESLYNALQS LRDREFSTFY ESLKYA RVK EVEEMCKRSL ESVYSLYPTL SRLQAIGELE SIGELFSRSV THRQLSEVYI KWQKHSQLLK DSDFSFQEPI MALRTVI LE ILMEKEMDNS QRECIKDILT KHLVELSILA RTFKNTQLPE RAIFQIKQYN SVSCGVSEWQ LEEAQVFWAK KEQSLALS I LKQMIKKLDA SCAANNPSLK LTYTECLRVC GNWLAETCLE NPAVIMQTYL EKAVEVAGNY DGESSDELRN GKMKAFLSL ARFSDTQYQR IENYMKSSEF ENKQALLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEL ALRALKEDRK RFLCKAVENY INCLLSGEE HDMWVFRLCS LWLENSGVSE VNGMMKRDGM KIPTYKFLPL MYQLAARMGT KMMGGLGFHE VLNNLISRIS M DHPHHTLF IILALANANR DEFLTKPEVA RRSRITKNVP KQSSQLDEDR TEAANRIICT IRSRRPQMVR SVEALCDAYI IL ANLDATQ WKTQRKGINI PADQPITKLK NLEDVVVPTM EIKVDHTGEY GNLVTIQSFK AEFRLAGGVN LPKIIDCVGS DGK ERRQLV KGRDDLRQDA VMQQVFQMCN TLLQRNTETR KRKLTICTYK VVPLSQRSGV LEWCTGTVPI GEFLVNNEDG AHKR YRPND FSAFQCQKKM MEVQKKSFEE KYEVFMDVCQ NFQPVFRYFC MEKFLDPAIW FEKRLAYTRS VATSSIVGYI LGLGD RHVQ NILINEQSAE LVHIDLGVAF EQGKILPTPE TVPFRLTRDI VDGMGITGVE GVFRRCCEKT MEVMRNSQET LLTIVE VLL YDPLFDWTMN PLKALYLQQR PEDETELHPT LNADDQECKR NLSDIDQSFN KVAERVLMRL QEKLKGVEEG TVLSVGG QV NLLIQQAIDP KNLSRLFPGW KAWV UniProtKB: Serine-protein kinase ATM |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.6 mg/mL | ||||||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil, UltrAuFoil, R1.2/1.3 / Material: GOLD / Mesh: 300 | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: HOMEMADE PLUNGER Details: 3 uL sample/grid blotted for 12 s before plunge-freezing. | ||||||||||||||||||
Details | The sample was purified by anti-FLAG affinity chromatography followed by overnight dialysis and a final gel-filtration. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 80.15 K |
Specialist optics | Energy filter - Name: GIF / Energy filter - Lower energy threshold: 0 eV / Energy filter - Upper energy threshold: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-20 / Number grids imaged: 4 / Number real images: 2720 / Average exposure time: 0.8 sec. / Average electron dose: 2.1 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated magnification: 35714 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 4.0 µm / Nominal defocus min: 2.5 µm / Nominal magnification: 97902 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-5np1: |