- EMDB-40660: Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the pr... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-40660
タイトル
Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the presence of telomeric ssDNA
マップデータ
Sharpened full map of human CST bound to POT1(ESDL)/TPP1 in the presence of telomeric ssDNA
試料
複合体: ssDNA-bound human CST-POT1(ESDL)/TPP1 complex
タンパク質・ペプチド: CST complex subunit CTC1
タンパク質・ペプチド: CST complex subunit STN1
タンパク質・ペプチド: CST complex subunit TEN1
タンパク質・ペプチド: Protection of telomeres protein 1
タンパク質・ペプチド: TPP1
DNA: DNA (5'-D(*TP*TP*AP*GP*GP*GP*TP*TP*AP*G)-3')
リガンド: ZINC ION
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 DNA strand elongation / positive regulation of telomeric D-loop disassembly / G-rich single-stranded DNA binding / telomere assembly / CST complex / segmentation / urogenital system development / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / protection from non-homologous end joining at telomere ...positive regulation of DNA strand elongation / positive regulation of telomeric D-loop disassembly / G-rich single-stranded DNA binding / telomere assembly / CST complex / segmentation / urogenital system development / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / protection from non-homologous end joining at telomere / regulation of double-strand break repair via nonhomologous end joining / telomerase inhibitor activity / DEAD/H-box RNA helicase binding / establishment of protein localization to telomere / regulation of establishment of protein localization to telomere / telomeric D-loop disassembly / shelterin complex / telomere maintenance via telomere lengthening / Telomere C-strand synthesis initiation / regulation of telomere maintenance via telomerase / Telomere C-strand (Lagging Strand) Synthesis / single-stranded telomeric DNA binding / nuclear telomere cap complex / G-rich strand telomeric DNA binding / telomere capping / intermediate filament cytoskeleton / 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 / telomerase holoenzyme complex / embryonic limb morphogenesis / bone marrow development / protein localization to chromosome, telomeric region / telomeric DNA binding / hematopoietic stem cell proliferation / negative regulation of telomere maintenance via telomerase / positive regulation of telomere maintenance / Telomere Extension By Telomerase / replicative senescence / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / telomere maintenance via telomerase / Packaging Of Telomere Ends / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / spleen development / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / regulation of G2/M transition of mitotic cell cycle / DNA polymerase binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / positive regulation of telomere maintenance via telomerase / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere maintenance / bioluminescence / thymus development / positive regulation of DNA replication / skeletal system development / generation of precursor metabolites and energy / intracellular protein transport / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / multicellular organism growth / DNA Damage/Telomere Stress Induced Senescence / host cell cytoplasmic vesicle membrane / fibrillar center / positive regulation of fibroblast proliferation / single-stranded DNA binding / nucleoside-triphosphate phosphatase / outer membrane-bounded periplasmic space / channel activity / monoatomic ion transmembrane transport / chromosome, telomeric region / DNA replication / RNA helicase activity / nuclear body / endocytosis involved in viral entry into host cell / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / intracellular membrane-bounded organelle / DNA-templated transcription / DNA damage response / protein-containing complex binding / virion attachment to host cell / host cell nucleus / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding 類似検索 - 分子機能
CST complex subunit Ten1, animal and plant type / CST complex subunit CTC1 / CST complex subunit CTC1-like / CST, telomere maintenance, complex subunit CTC1 / Telomere-capping, CST complex subunit / CST complex subunit Stn1 / Stn1, C-terminal / CST complex subunit Stn1, wHTH1 motif superfamily / CST, complex subunit STN1, C terminal / : ...CST complex subunit Ten1, animal and plant type / CST complex subunit CTC1 / CST complex subunit CTC1-like / CST, telomere maintenance, complex subunit CTC1 / Telomere-capping, CST complex subunit / CST complex subunit Stn1 / Stn1, C-terminal / CST complex subunit Stn1, wHTH1 motif superfamily / CST, complex subunit STN1, C terminal / : / Protection of telomeres protein 1 (POT1), C-terminal insertion domain / Shelterin complex subunit TPP1/Est3 / Shelterin complex subunit, TPP1/ACD / Adrenocortical dysplasia protein / Protection of telomeres protein 1, ssDNA-binding domain / ssDNA-binding domain of telomere protection protein / Replication factor A protein-like / Protection of telomeres protein 1 / Telomeric single stranded DNA binding POT1/Cdc13 / Telomeric single stranded DNA binding POT1/CDC13 / Telomeric single stranded DNA binding POT1/CDC13 / OB-fold nucleic acid binding domain, AA-tRNA synthetase-type / OB-fold nucleic acid binding domain / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / Winged helix DNA-binding domain superfamily / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Reverse transcriptase/Diguanylate cyclase domain / Winged helix-like DNA-binding domain superfamily / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Genome polyprotein / Maltose/maltodextrin-binding periplasmic protein / CST complex subunit CTC1 / CST complex subunit TEN1 / Adrenocortical dysplasia protein homolog / CST complex subunit STN1 / Protection of telomeres protein 1 類似検索 - 構成要素
National Institutes of Health/National Cancer Institute (NIH/NCI)
R35 CA210036
米国
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.