- 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 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
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 / Green fluorescent protein, GFP / Bacterial extracellular solute-binding protein / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent 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) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / 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 / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Winged helix DNA-binding domain superfamily / Reverse transcriptase/Diguanylate cyclase domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Winged helix-like DNA-binding domain superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Nucleic acid-binding, OB-fold / 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.