- EMDB-26866: Tetrahymena CST with Polymerase alpha-Primase -
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基本情報
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データベース: EMDB / ID: EMD-26866
タイトル
Tetrahymena CST with Polymerase alpha-Primase
マップデータ
full map
試料
複合体: Tetrahymena CST-PolaPrim
複合体: Tetrahymena CST
タンパク質・ペプチド: Telomerase-associated protein of 75 kDa
タンパク質・ペプチド: Telomerase-associated protein of 45 kDa
タンパク質・ペプチド: Telomerase-associated protein of 19 kDa
タンパク質・ペプチド: Telomerase associated protein p50
DNA: Telomere DNA
複合体: Tetrahymena DNA polymerase alpha-primase
タンパク質・ペプチド: DNA polymerase
リガンド: ZINC ION
キーワード
telomerase / RNP / CST / polymerase / REPLICATION
機能・相同性
機能・相同性情報
alpha DNA polymerase:primase complex / lagging strand elongation / mitotic DNA replication initiation / telomerase holoenzyme complex / leading strand elongation / DNA replication origin binding / telomere maintenance via telomerase / single-stranded DNA binding / chromosome, telomeric region / DNA-directed DNA polymerase ...alpha DNA polymerase:primase complex / lagging strand elongation / mitotic DNA replication initiation / telomerase holoenzyme complex / leading strand elongation / DNA replication origin binding / telomere maintenance via telomerase / single-stranded DNA binding / chromosome, telomeric region / DNA-directed DNA polymerase / DNA-directed DNA polymerase activity / nucleotide binding / chromatin binding / metal ion binding 類似検索 - 分子機能
DNA polymerase alpha catalytic subunit, catalytic domain / DNA polymerase family B, thumb domain / DNA polymerase family B signature. / DNA-directed DNA polymerase, family B, conserved site / DNA polymerase family B / DNA polymerase family B, exonuclease domain / DNA-directed DNA polymerase, family B, exonuclease domain / DNA-directed DNA polymerase, family B, multifunctional domain / DNA polymerase, palm domain superfamily / DNA polymerase type-B family ...DNA polymerase alpha catalytic subunit, catalytic domain / DNA polymerase family B, thumb domain / DNA polymerase family B signature. / DNA-directed DNA polymerase, family B, conserved site / DNA polymerase family B / DNA polymerase family B, exonuclease domain / DNA-directed DNA polymerase, family B, exonuclease domain / DNA-directed DNA polymerase, family B, multifunctional domain / DNA polymerase, palm domain superfamily / DNA polymerase type-B family / DNA-directed DNA polymerase, family B / Ribonuclease H superfamily / Ribonuclease H-like superfamily / DNA/RNA polymerase superfamily 類似検索 - ドメイン・相同性
Telomerase-associated protein of 75 kDa / Telomerase-associated protein of 19 kDa / Telomerase-associated protein of 50 kDa / DNA polymerase / Telomerase-associated protein of 45 kDa 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM131901
米国
National Science Foundation (NSF, United States)
MCB2016540
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM071940
米国
引用
ジャーナル: Nature / 年: 2022 タイトル: Structure of Tetrahymena telomerase-bound CST with polymerase α-primase. 著者: Yao He / He Song / Henry Chan / Baocheng Liu / Yaqiang Wang / Lukas Sušac / Z Hong Zhou / Juli Feigon / 要旨: Telomeres are the physical ends of linear chromosomes. They are composed of short repeating sequences (such as TTGGGG in the G-strand for Tetrahymena thermophila) of double-stranded DNA with a single- ...Telomeres are the physical ends of linear chromosomes. They are composed of short repeating sequences (such as TTGGGG in the G-strand for Tetrahymena thermophila) of double-stranded DNA with a single-strand 3' overhang of the G-strand and, in humans, the six shelterin proteins: TPP1, POT1, TRF1, TRF2, RAP1 and TIN2. TPP1 and POT1 associate with the 3' overhang, with POT1 binding the G-strand and TPP1 (in complex with TIN2) recruiting telomerase via interaction with telomerase reverse transcriptase (TERT). The telomere DNA ends are replicated and maintained by telomerase, for the G-strand, and subsequently DNA polymerase α-primase (PolαPrim), for the C-strand. PolαPrim activity is stimulated by the heterotrimeric complex CTC1-STN1-TEN1 (CST), but the structural basis of the recruitment of PolαPrim and CST to telomere ends remains unknown. Here we report cryo-electron microscopy (cryo-EM) structures of Tetrahymena CST in the context of the telomerase holoenzyme, in both the absence and the presence of PolαPrim, and of PolαPrim alone. Tetrahymena Ctc1 binds telomerase subunit p50, a TPP1 orthologue, on a flexible Ctc1 binding motif revealed by cryo-EM and NMR spectroscopy. The PolαPrim polymerase subunit POLA1 binds Ctc1 and Stn1, and its interface with Ctc1 forms an entry port for G-strand DNA to the POLA1 active site. We thus provide a snapshot of four key components that are required for telomeric DNA synthesis in a single active complex-telomerase-core ribonucleoprotein, p50, CST and PolαPrim-that provides insights into the recruitment of CST and PolαPrim and the handoff between G-strand and C-strand synthesis.