+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-40659 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | |||||||||
マップデータ | Sharpened full map of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | |||||||||
試料 |
| |||||||||
キーワード | telomere / shelterin / cst / complex / DNA BINDING PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 positive regulation of single-stranded telomeric DNA binding / positive regulation of DNA strand elongation / regulation of DNA helicase activity / positive regulation of DNA helicase activity / G-rich single-stranded DNA binding / telomere assembly / CST complex / segmentation / urogenital system development / 8-hydroxy-2'-deoxyguanosine DNA binding ...positive regulation of single-stranded telomeric DNA binding / positive regulation of DNA strand elongation / regulation of DNA helicase activity / positive regulation of DNA helicase activity / G-rich single-stranded DNA binding / telomere assembly / CST complex / segmentation / urogenital system development / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / regulation of double-strand break repair via nonhomologous end joining / positive regulation of helicase activity / protection from non-homologous end joining at telomere / telomerase inhibitor activity / DEAD/H-box RNA helicase binding / establishment of protein localization to telomere / telomere maintenance via telomere lengthening / telomeric D-loop disassembly / shelterin complex / Telomere C-strand synthesis initiation / regulation of telomere maintenance via telomerase / Telomere C-strand (Lagging Strand) Synthesis / : / positive regulation of telomere maintenance / nuclear telomere cap complex / single-stranded telomeric DNA binding / Processive synthesis on the C-strand of the telomere / Polymerase switching on the C-strand of the telomere / Removal of the Flap Intermediate from the C-strand / G-rich strand telomeric DNA binding / telomere capping / telomerase holoenzyme complex / bone marrow development / embryonic limb morphogenesis / DNA duplex unwinding / intermediate filament cytoskeleton / protein localization to chromosome, telomeric region / hematopoietic stem cell proliferation / telomeric DNA binding / : / negative regulation of telomere maintenance via telomerase / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / Telomere Extension By Telomerase / carbohydrate transmembrane transporter activity / telomere maintenance via telomerase / maltose binding / replicative senescence / maltose transport / maltodextrin transmembrane transport / DNA polymerase binding / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / spleen development / positive regulation of telomere maintenance via telomerase / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / regulation of G2/M transition of mitotic cell cycle / Inhibition of DNA recombination at telomere / Meiotic synapsis / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / telomere maintenance / symbiont genome entry into host cell via pore formation in plasma membrane / bioluminescence / picornain 3C / thymus development / T=pseudo3 icosahedral viral capsid / positive regulation of DNA replication / generation of precursor metabolites and energy / skeletal system development / host cell cytoplasmic vesicle membrane / intracellular protein transport / cytoplasmic vesicle membrane / multicellular organism growth / endocytosis involved in viral entry into host cell / DNA Damage/Telomere Stress Induced Senescence / fibrillar center / positive regulation of fibroblast proliferation / symbiont-mediated suppression of host gene expression / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / outer membrane-bounded periplasmic space / single-stranded DNA binding / chromosome, telomeric region / RNA helicase activity / nuclear body / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / intracellular membrane-bounded organelle / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / DNA damage response / host cell nucleus 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
データ登録者 | Cai SW | |||||||||
資金援助 | 米国, 2件
| |||||||||
引用 | ジャーナル: bioRxiv / 年: 2023 タイトル: POT1 recruits and regulates CST-Polα/Primase at human telomeres. 著者: Sarah W Cai / Hiroyuki Takai / Thomas Walz / Titia de Lange / 要旨: 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. | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_40659.map.gz | 157.2 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-40659-v30.xml emd-40659.xml | 20.6 KB 20.6 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_40659_fsc.xml | 11.7 KB | 表示 | FSCデータファイル |
画像 | emd_40659.png | 125.8 KB | ||
マスクデータ | emd_40659_msk_1.map | 166.4 MB | マスクマップ | |
Filedesc metadata | emd-40659.cif.gz | 8.1 KB | ||
その他 | emd_40659_half_map_1.map.gz emd_40659_half_map_2.map.gz | 154.6 MB 154.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-40659 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40659 | HTTPS FTP |
-関連構造データ
関連構造データ | 8sojMC 8sokC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_40659.map.gz / 形式: CCP4 / 大きさ: 166.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Sharpened full map of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.86 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-マスク #1
ファイル | emd_40659_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: Half map A of human CST bound to...
ファイル | emd_40659_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Half map A of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: Half map B of human CST bound to...
ファイル | emd_40659_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Half map B of human CST bound to POT1(ESDL)/TPP1 in the absence of telomeric ssDNA | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
-全体 : Human CST-POT1(ESDL)/TPP1 complex
全体 | 名称: Human CST-POT1(ESDL)/TPP1 complex |
---|---|
要素 |
|
-超分子 #1: Human CST-POT1(ESDL)/TPP1 complex
超分子 | 名称: Human CST-POT1(ESDL)/TPP1 complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 / 詳細: CST-POT1(ESDL)/TPP1 complex in the absence of DNA |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 380 KDa |
-分子 #1: CST complex subunit CTC1
分子 | 名称: CST complex subunit CTC1 / タイプ: protein_or_peptide / ID: 1 / 詳細: His6-MBP-3C tagged human Ctc1 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 178.300609 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MGSSHHHHHH SSGTKIEEGK LVIWINGDKG YNGLAEVGKK FEKDTGIKVT VEHPDKLEEK FPQVAATGDG PDIIFWAHDR FGGYAQSGL LAEITPDKAF QDKLYPFTWD AVRYNGKLIA YPIAVEALSL IYNKDLLPNP PKTWEEIPAL DKELKAKGKS A LMFNLQEP ...文字列: 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, CST complex subunit CTC1 |
-分子 #2: CST complex subunit STN1
分子 | 名称: CST complex subunit STN1 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO / EC番号: picornain 2A |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 115.627211 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MWSHPQFEKG GGSGGGSGGS AWSHPQFEKG SVSKGEELFT GVVPILVELD GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWP TLVTTLTYGV QCFSRYPDHM KQHDFFKSAM PEGYVQERTI FFKDDGNYKT RAEVKFEGDT LVNRIELKGI D FKEDGNIL ...文字列: 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, CST complex subunit STN1 |
-分子 #3: CST complex subunit TEN1
分子 | 名称: CST complex subunit TEN1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 13.872013 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MMLPKPGTYY LPWEVSAGQV PDGSTLRTFG RLCLYDMIQS RVTLMAQHGS DQHQVLVCTK LVEPFHAQVG SLYIVLGELQ HQQDRGSVV KARVLTCVEG MNLPLLEQAI REQRLYKQER GGSQ UniProtKB: CST complex subunit TEN1 |
-分子 #4: Protection of telomeres protein 1
分子 | 名称: Protection of telomeres protein 1 / タイプ: protein_or_peptide / ID: 4 詳細: mPOT1b residues ESDL 323-326 are inserted into the human POT1 sequence between S320 and V321 コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 72.938219 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MHHHHHHGSS LVPATNYIYT PLNQLKGGTI VNVYGVVKFF KPPYLSKGTD YCSVVTIVDQ TNVKLTCLLF SGNYEALPII YKNGDIVRF HRLKIQVYKK ETQGITSSGF ASLTFEGTLG APIIPRTSSK YFNFTTEDHK MVEALRVWAS THMSPSWTLL K LCDVQPMQ ...文字列: 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 |
-分子 #5: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 5 / コピー数: 2 / 式: ZN |
---|---|
分子量 | 理論値: 65.409 Da |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 0.05 mg/mL |
---|---|
緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.3 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |