- EMDB-31811: catalytic core of human telomerase holoenzyme -
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基本情報
登録情報
データベース: EMDB / ID: EMD-31811
タイトル
catalytic core of human telomerase holoenzyme
マップデータ
試料
複合体: Catalytic core
タンパク質・ペプチド: Telomerase reverse transcriptase
タンパク質・ペプチド: Histone H2A type 1-B/E
タンパク質・ペプチド: Histone H2B type 1-K
RNA: Telomerase RNA component
DNA: Primer DNA
機能・相同性
機能・相同性情報
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 / telomerase catalytic core complex / RNA-templated DNA biosynthetic process ...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 / telomerase catalytic core complex / RNA-templated DNA biosynthetic process / : / establishment of protein localization to telomere / telomerase activity / nuclear telomere cap complex / siRNA processing / telomerase holoenzyme complex / positive regulation of vascular associated smooth muscle cell migration / telomerase RNA binding / DNA biosynthetic process / RNA-templated transcription / telomeric DNA binding / positive regulation of stem cell proliferation / mitochondrial nucleoid / negative regulation of cellular senescence / Telomere Extension By Telomerase / telomere maintenance via telomerase / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / replicative senescence / positive regulation of Wnt signaling pathway / positive regulation of G1/S transition of mitotic cell cycle / protein localization to CENP-A containing chromatin / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / negative regulation of endothelial cell apoptotic process / response to cadmium ion / heterochromatin organization / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / positive regulation of vascular associated smooth muscle cell proliferation / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / RNA Polymerase I Promoter Opening / telomere maintenance / Assembly of the ORC complex at the origin of replication / mitochondrion organization / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / PRC2 methylates histones and DNA / innate immune response in mucosa / positive regulation of nitric-oxide synthase activity / Defective pyroptosis / HDACs deacetylate histones / positive regulation of glucose import / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / regulation of protein stability / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / PML body / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / transcription coactivator binding / positive regulation of miRNA transcription / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / RNA-directed DNA polymerase / structural constituent of chromatin / positive regulation of angiogenesis / antimicrobial humoral immune response mediated by antimicrobial peptide / UCH proteinases / RNA-directed DNA polymerase activity / nucleosome / positive regulation of protein binding / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / Processing of DNA double-strand break ends / protein-folding chaperone binding / antibacterial humoral response / cellular response to hypoxia 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: Cell Res / 年: 2021 タイトル: Zipper head mechanism of telomere synthesis by human telomerase. 著者: Futang Wan / Yongbo Ding / Yuebin Zhang / Zhenfang Wu / Shaobai Li / Lin Yang / Xiangyu Yan / Pengfei Lan / Guohui Li / Jian Wu / Ming Lei / 要旨: Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment ...Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template. Despite recent structural characterizations of human and Tetrahymena telomerase, it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA. Here, we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Å and 3.9 Å for the catalytic core and biogenesis module, respectively. The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase (TERT) catalytic subunit functions as a zipper head to limit the length of the short primer-template duplex in the active center. Moreover, our structural and computational analyses suggest that TERT and telomerase RNA (hTR) are organized to harbor a preformed active site that can accommodate short primer-template duplex substrates for catalysis. Furthermore, our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase. We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary. Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis. In addition, we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases. Together, our study provides an integrated model for telomerase-mediated telomere synthesis.