- EMDB-14199: Refined, unsharpened map of human telomerase-DNA-TPP1-POT1 complex -
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基本情報
登録情報
データベース: EMDB / ID: EMD-14199
タイトル
Refined, unsharpened map of human telomerase-DNA-TPP1-POT1 complex
マップデータ
Refined unsharpened map of telomerase-TPP1-Pot1-DNA
試料
複合体: Complex of telomeric DNA-bound human telomerase with TPP1 and Pot1
タンパク質・ペプチド: Telomerase reverse transcriptase
タンパク質・ペプチド: Histone H2A
タンパク質・ペプチド: Histone H2B
タンパク質・ペプチド: TPP1
タンパク質・ペプチド: POT1
RNA: human telomerase RNA
DNA: Telomeric DNA
キーワード
Reverse transcriptase / ribonucleoprotein / telomerase / telomere / DNA BINDING PROTEIN
機能・相同性
機能・相同性情報
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 / positive regulation of hair cycle / template-free RNA nucleotidyltransferase / positive regulation of transdifferentiation / TERT-RMRP complex / DNA strand elongation ...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 / positive regulation of hair cycle / template-free RNA nucleotidyltransferase / positive regulation of transdifferentiation / TERT-RMRP complex / DNA strand elongation / RNA-directed RNA polymerase complex / positive regulation of protein localization to nucleolus / siRNA transcription / 8-hydroxy-2'-deoxyguanosine DNA binding / telomerase catalytic core complex / telomeric D-loop binding / regulation of double-strand break repair via nonhomologous end joining / telomerase activity / positive regulation of helicase activity / Regulation of MITF-M-dependent genes involved in DNA damage repair and senescence / : / telomerase inhibitor activity / DEAD/H-box RNA helicase binding / RNA-templated DNA biosynthetic process / establishment of protein localization to telomere / 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 / single-stranded telomeric DNA binding / nuclear telomere cap complex / Processive synthesis on the C-strand of the telomere / siRNA processing / 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 / Telomere Extension By Telomerase / positive regulation of vascular associated smooth muscle cell migration / telomerase holoenzyme complex / telomerase RNA binding / DNA duplex unwinding / positive regulation of G1/S transition of mitotic cell cycle / telomeric DNA binding / DNA biosynthetic process / RNA-templated transcription / positive regulation of stem cell proliferation / mitochondrial nucleoid / : / negative regulation of cellular senescence / negative regulation of telomere maintenance via telomerase / telomere maintenance via telomerase / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of Wnt signaling pathway / replicative senescence / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / negative regulation of endothelial cell apoptotic process / response to cadmium ion / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Meiotic synapsis / Inhibition of DNA recombination at telomere / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of telomere maintenance via telomerase / telomere maintenance / positive regulation of miRNA transcription / mitochondrion organization / DNA Damage/Telomere Stress Induced Senescence / positive regulation of nitric-oxide synthase activity / positive regulation of glucose import / Formation of the beta-catenin:TCF transactivating complex / regulation of protein stability / PML body / transcription coactivator binding / RNA-directed DNA polymerase / structural constituent of chromatin / positive regulation of angiogenesis / RNA-directed DNA polymerase activity / nucleosome / positive regulation of protein binding / cellular response to hypoxia / protein-folding chaperone binding / chromosome, telomeric region / negative regulation of neuron apoptotic process / tRNA binding / nuclear body / nuclear speck / protein heterodimerization activity / negative regulation of gene expression / RNA-dependent RNA polymerase activity / nucleolus / protein homodimerization activity / DNA binding / RNA binding / nucleoplasm 類似検索 - 分子機能
: / Protection of telomeres protein 1 (POT1), C-terminal insertion domain / Shelterin complex subunit TPP1/Est3 / Shelterin complex subunit, TPP1/ACD / Adrenocortical dysplasia protein / : / Telomerase reverse transcriptase, C-terminal extension / Protection of telomeres protein 1, ssDNA-binding domain / ssDNA-binding domain of telomere protection protein / Protection of telomeres protein 1 ...: / Protection of telomeres protein 1 (POT1), C-terminal insertion domain / Shelterin complex subunit TPP1/Est3 / Shelterin complex subunit, TPP1/ACD / Adrenocortical dysplasia protein / : / Telomerase reverse transcriptase, C-terminal extension / Protection of telomeres protein 1, ssDNA-binding domain / ssDNA-binding domain of telomere protection protein / Protection of telomeres protein 1 / Telomerase ribonucleoprotein complex - RNA binding domain / Telomeric single stranded DNA binding POT1/Cdc13 / Telomeric single stranded DNA binding POT1/CDC13 / Telomeric single stranded DNA binding POT1/CDC13 / Telomerase reverse transcriptase / Telomerase ribonucleoprotein complex - RNA-binding domain / Telomerase ribonucleoprotein complex - RNA binding domain / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone H2A / Histone 2A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase domain / Reverse transcriptase (RT) catalytic domain profile. / Histone-fold / Nucleic acid-binding, OB-fold / DNA/RNA polymerase superfamily 類似検索 - ドメイン・相同性
ジャーナル: Science / 年: 2022 タイトル: Structural basis of human telomerase recruitment by TPP1-POT1. 著者: Zala Sekne / George E Ghanim / Anne-Marie M van Roon / Thi Hoang Duong Nguyen / 要旨: Telomerase maintains genome stability by extending the 3' telomeric repeats at eukaryotic chromosome ends, thereby counterbalancing progressive loss caused by incomplete genome replication. In ...Telomerase maintains genome stability by extending the 3' telomeric repeats at eukaryotic chromosome ends, thereby counterbalancing progressive loss caused by incomplete genome replication. In mammals, telomerase recruitment to telomeres is mediated by TPP1, which assembles as a heterodimer with POT1. We report structures of DNA-bound telomerase in complex with TPP1 and with TPP1-POT1 at 3.2- and 3.9-angstrom resolution, respectively. Our structures define interactions between telomerase and TPP1-POT1 that are crucial for telomerase recruitment to telomeres. The presence of TPP1-POT1 stabilizes the DNA, revealing an unexpected path by which DNA exits the telomerase active site and a DNA anchor site on telomerase that is important for telomerase processivity. Our findings rationalize extensive prior genetic and biochemical findings and provide a framework for future mechanistic work on telomerase regulation.