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- EMDB-40659: Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the ab... -
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Open data
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Basic information
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Title | Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | |||||||||
![]() | Sharpened full map of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | |||||||||
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Function / homology | ![]() positive regulation of single-stranded telomeric DNA binding / positive regulation of DNA strand elongation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
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Method | ![]() ![]() | |||||||||
![]() | Cai SW | |||||||||
Funding support | ![]()
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![]() | ![]() Title: POT1 recruits and regulates CST-Polα/Primase at human telomeres. Authors: Sarah W Cai / Hiroyuki Takai / Thomas Walz / Titia de Lange / ![]() Abstract: Telomere maintenance requires extension of the G-rich telomeric repeat strand by telomerase and fill-in synthesis of the C-rich strand by Polα/Primase. Telomeric Polα/Primase is bound to Ctc1-Stn1- ...Telomere maintenance requires extension of the G-rich telomeric repeat strand by telomerase and fill-in synthesis of the C-rich strand by Polα/Primase. Telomeric Polα/Primase is bound to Ctc1-Stn1-Ten1 (CST), a single-stranded DNA-binding complex. Like mutations in telomerase, mutations affecting CST-Polα/Primase result in pathological telomere shortening and cause a telomere biology disorder, Coats plus (CP). We determined cryogenic electron microscopy structures of human CST bound to the shelterin heterodimer POT1/TPP1 that reveal how CST is recruited to telomeres by POT1. Phosphorylation of POT1 is required for CST recruitment, and the complex is formed through conserved interactions involving several residues mutated in CP. Our structural and biochemical data suggest that phosphorylated POT1 holds CST-Polα/Primase in an inactive auto-inhibited state until telomerase has extended the telomere ends. We propose that dephosphorylation of POT1 releases CST-Polα/Primase into an active state that completes telomere replication through fill-in synthesis. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 157.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.6 KB 20.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.7 KB | Display | ![]() |
Images | ![]() | 125.8 KB | ||
Masks | ![]() | 166.4 MB | ![]() | |
Filedesc metadata | ![]() | 8.1 KB | ||
Others | ![]() ![]() | 154.6 MB 154.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8sojMC ![]() 8sokC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 | Sharpened full map of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: Half map A of human CST bound to...
File | emd_40659_half_map_1.map | ||||||||||||
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Annotation | Half map A of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B of human CST bound to...
File | emd_40659_half_map_2.map | ||||||||||||
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Annotation | Half map B of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human CST-POT1(ESDL)/TPP1 complex
Entire | Name: Human CST-POT1(ESDL)/TPP1 complex |
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Components |
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-Supramolecule #1: Human CST-POT1(ESDL)/TPP1 complex
Supramolecule | Name: Human CST-POT1(ESDL)/TPP1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 / Details: CST-POT1(ESDL)/TPP1 complex in the absence of DNA |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 380 KDa |
-Macromolecule #1: CST complex subunit CTC1
Macromolecule | Name: CST complex subunit CTC1 / type: protein_or_peptide / ID: 1 / Details: His6-MBP-3C tagged human Ctc1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 178.300609 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSSHHHHHH SSGTKIEEGK LVIWINGDKG YNGLAEVGKK FEKDTGIKVT VEHPDKLEEK FPQVAATGDG PDIIFWAHDR FGGYAQSGL LAEITPDKAF QDKLYPFTWD AVRYNGKLIA YPIAVEALSL IYNKDLLPNP PKTWEEIPAL DKELKAKGKS A LMFNLQEP ...String: MGSSHHHHHH SSGTKIEEGK LVIWINGDKG YNGLAEVGKK FEKDTGIKVT VEHPDKLEEK FPQVAATGDG PDIIFWAHDR FGGYAQSGL LAEITPDKAF QDKLYPFTWD AVRYNGKLIA YPIAVEALSL IYNKDLLPNP PKTWEEIPAL DKELKAKGKS A LMFNLQEP YFTWPLIAAD GGYAFKYENG KYDIKDVGVD NAGAKAGLTF LVDLIKNKHM NADTDYSIAE AAFNKGETAM TI NGPWAWS NIDTSKVNYG VTVLPTFKGQ PSKPFVGVLS AGINAASPNK ELAKEFLENY LLTDEGLEAV NKDKPLGAVA LKS YEEELA KDPRIAATME NAQKGEIMPN IPQMSAFWYA VRTAVINAAS GRQTVDEALK DAQTKLVEKY LEVLFQGPGS MAAG RAQVP SSEQAWLEDA QVFIQKTLCP AVKEPNVQLT PLVIDCVKTV WLSQGRNQGS TLPLSYSFVS VQDLKTHQRL PCCSH LSWS SSAYQAWAQE AGPNGNPLPR EQLLLLGTLT DLSADLEQEC RNGSLYVRDN TGVLSCELID LDLSWLGHLF LFPRWS YLP PARWNSSGEG HLELWDAPVP VFPLTISPGP VTPIPVLYPE SASCLLRLRN KLRGVQRNLA GSLVRLSALV KSKQKAY FI LSLGRSHPAV THVSIIVQVP AQLVWHRALR PGTAYVLTEL RVSKIRGQRQ HVWMTSQSSR LLLLKPECVQ ELELELEG P LLEADPKPLP MPSNSEDKKD PESLVRYSRL LSYSGAVTGV LNEPAGLYEL DGQLGLCLAY QQFRGLRRVM RPGVCLQLQ DVHLLQSVGG GTRRPVLAPC LRGAVLLQSF SRQKPGAHSS RQAYGASLYE QLVWERQLGL PLYLWATKAL EELACKLCPH VLRHHQFLQ HSSPGSPSLG LQLLAPTLDL LAPPGSPVRN AHNEILEEPH HCPLQKYTRL QTPSSFPTLA TLKEEGQRKA W ASFDPKAL LPLPEASYLP SCQLNRRLAW SWLCLLPSAF CPAQVLLGVL VASSHKGCLQ LRDQSGSLPC LLLAKHSQPL SD PRLIGCL VRAERFQLIV ERDVRSSFPS WKELSMPGFI QKQQARVYVQ FFLADALILP VPRPCLHSAT PSTPQTDPTG PEG PHLGQS RLFLLCHKEA LMKRNFCVPP GASPEVPKPA LSFYVLGSWL GGTQRKEGTG WGLPEPQGND DNDQKVHLIF FGSS VRWFE FLHPGQVYRL IAPGPATPML FEKDGSSCIS RRPLELAGCA SCLTVQDNWT LELESSQDIQ DVLDANKSLP ESSLT DLLS DNFTDSLVSF SAEILSRTLC EPLVASLWMK LGNTGAMRRC VKLTVALETA ECEFPPHLDV YIEDPHLPPS LGLLPG ARV HFSQLEKRVS RSHNVYCCFR SSTYVQVLSF PPETTISIPL PHIYLAELLQ GGQSPFQATA SCHIVSVFSL QLFWVCA YC TSICRQGKCT RLGSTCPTQT AISQAIIRLL VEDGTAEAVV TCRNHHVAAA LGLCPREWAS LLDFVQVPGR VVLQFAGP G AQLESSARVD EPMTMFLWTL CTSPSVLRPI VLSFELERKP SKIVPLEPPR LQRFQCGELP FLTHVNPRLR LSCLSIRES EYSSSLGILA SSC UniProtKB: Maltose/maltodextrin-binding periplasmic protein, ![]() |
-Macromolecule #2: CST complex subunit STN1
Macromolecule | Name: CST complex subunit STN1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 115.627211 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MWSHPQFEKG GGSGGGSGGS AWSHPQFEKG SVSKGEELFT GVVPILVELD GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWP TLVTTLTYGV QCFSRYPDHM KQHDFFKSAM PEGYVQERTI FFKDDGNYKT RAEVKFEGDT LVNRIELKGI D FKEDGNIL ...String: MWSHPQFEKG GGSGGGSGGS AWSHPQFEKG SVSKGEELFT GVVPILVELD GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWP TLVTTLTYGV QCFSRYPDHM KQHDFFKSAM PEGYVQERTI FFKDDGNYKT RAEVKFEGDT LVNRIELKGI D FKEDGNIL GHKLEYNYNS HNVYIMADKQ KNGIKVNFKI RHNIEDGSVQ LADHYQQNTP IGDGPVLLPD NHYLSTQSAL SK DPNEKRD HMVLLEFVTA AGITLGMDEL YKENLYFQGG SMAGSGRLVL RPWIRELILG SETPSSPRAG QLLEVLQDAE AAV AGPSHA PDTSDVGATL LVSDGTHSVR CLVTREALDT SDWEEKEFGF RGTEGRLLLL QDCGVHVQVA EGGAPAEFYL QVDR FSLLP TEQPRLRVPG CNQDLDVQKK LYDCLEEHLS ESTSSNAGLS LSQLLDEMRE DQEHQGALVC LAESCLTLEG PCTAP PVTH WAASRCKATG EAVYTVPSSM LCISENDQLI LSSLGPCQRT QGPELPPPDP ALQDLSLTLI ASPPSSPSSS GTPALP GHM SSEESGTSIS LLPALSLAAP DPGQRSSSQP SPAICSAPAT LTPRSPHASR TPSSPLQSCT PSLSPRSHVP SPHQALV TR PQKPSLEFKE FVGLPCKNRP PFPRTGATRG AQEGGSGGSM QPGSSRCEEE TPSLLWGLDP VFLAFAKLYI RDILDMKE S RQVPGVFLYN GHPIKQVDVL GTVIGVRERD AFYSYGVDDS TGVINCICWK KLNTESVSAA PSAARELSLT SQLKKLQET IEQKTKIEIG DTIRVRGSIR TYREEREIHA TTYYKVDDPV WNIQIARMLE LPTIYRKVYD QPFHSSALEK EEALSNPGAL DLPSLTSLL SEKAKEFLME NRVQSFYQQE LEMVESLLSL ANQPVIHSAS SDQVNFKKDT TSKAIHSIFK NAIQLLQEKG L VFQKDDGF DNLYYVTRED KDLHRKIHRI IQQDCQKPNH MEKGCHFLHI LACARLSIRP GLSEAVLQQV LELLEDQSDI VS TMEHYYT AF UniProtKB: Genome polyprotein, Adrenocortical dysplasia protein homolog, ![]() |
-Macromolecule #3: CST complex subunit TEN1
Macromolecule | Name: CST complex subunit TEN1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 13.872013 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MMLPKPGTYY LPWEVSAGQV PDGSTLRTFG RLCLYDMIQS RVTLMAQHGS DQHQVLVCTK LVEPFHAQVG SLYIVLGELQ HQQDRGSVV KARVLTCVEG MNLPLLEQAI REQRLYKQER GGSQ UniProtKB: ![]() |
-Macromolecule #4: Protection of telomeres protein 1
Macromolecule | Name: Protection of telomeres protein 1 / type: protein_or_peptide / ID: 4 Details: mPOT1b residues ESDL 323-326 are inserted into the human POT1 sequence between S320 and V321 Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 72.938219 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHGSS LVPATNYIYT PLNQLKGGTI VNVYGVVKFF KPPYLSKGTD YCSVVTIVDQ TNVKLTCLLF SGNYEALPII YKNGDIVRF HRLKIQVYKK ETQGITSSGF ASLTFEGTLG APIIPRTSSK YFNFTTEDHK MVEALRVWAS THMSPSWTLL K LCDVQPMQ ...String: MHHHHHHGSS LVPATNYIYT PLNQLKGGTI VNVYGVVKFF KPPYLSKGTD YCSVVTIVDQ TNVKLTCLLF SGNYEALPII YKNGDIVRF HRLKIQVYKK ETQGITSSGF ASLTFEGTLG APIIPRTSSK YFNFTTEDHK MVEALRVWAS THMSPSWTLL K LCDVQPMQ YFDLTCQLLG KAEVDGASFL LKVWDGTRTP FPSWRVLIQD LVLEGDLSHI HRLQNLTIDI LVYDNHVHVA RS LKVGSFL RIYSLHTKLQ SMNSENQTML SLEFHLHGGT SYGRGIRVLP ESNSDVDQLK KDLESANLTA NQHSDVICQS EPD DSFPSS GSESDLVSLY EVERCQQLSA TILTDHQYLE RTPLCAILKQ KAPQQYRIRA KLRSYKPRRL FQSVKLHCPK CHLL QEVPH EGDLDIIFQD GATKTPDVKL QNTSLYDSKI WTTKNQKGRK VAVHFVKNNG ILPLSNECLL LIEGGTLSEI CKLSN KFNS VIPVRSGHED LELLDLSAPF LIQGTIHHYG CKQCSSLRSI QNLNSLVDKT SWIPSSVAEA LGIVPLQYVF VMTFTL DDG TGVLEAYLMD SDKFFQIPAS EVLMDDDLQK SVDMIMDMFC PPGIKIDAYP WLECFIKSYN VTNGTDNQIC YQIFDTT VA EDVI UniProtKB: Protection of telomeres protein 1 |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 0.05 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.3 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |