EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structure of active human telomerase with telomere shelterin protein TPP1.
ジャーナル・号・ページ	Nature, Vol. 604, Issue 7906, Page 578-583, Year 2022
掲載日	2022年4月13日
著者	Baocheng Liu / Yao He / Yaqiang Wang / He Song / Z Hong Zhou / Juli Feigon /
PubMed 要旨	Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG. Its activity is a determinant of cancer ...Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG. Its activity is a determinant of cancer progression, stem cell renewal and cellular aging. Telomerase is recruited to telomeres and activated for telomere repeat synthesis by the telomere shelterin protein TPP1. Human telomerase has a bilobal structure with a catalytic core ribonuclear protein and a H and ACA box ribonuclear protein. Here we report cryo-electron microscopy structures of human telomerase catalytic core of telomerase reverse transcriptase (TERT) and telomerase RNA (TER (also known as hTR)), and of telomerase with the shelterin protein TPP1. TPP1 forms a structured interface with the TERT-unique telomerase essential N-terminal domain (TEN) and the telomerase RAP motif (TRAP) that are unique to TERT, and conformational dynamics of TEN-TRAP are damped upon TPP1 binding, defining the requirements for recruitment and activation. The structures further reveal that the elements of TERT and TER that are involved in template and telomeric DNA handling-including the TEN domain and the TRAP-thumb helix channel-are largely structurally homologous to those in Tetrahymena telomerase, and provide unique insights into the mechanism of telomerase activity. The binding site of the telomerase inhibitor BIBR1532 overlaps a critical interaction between the TER pseudoknot and the TERT thumb domain. Numerous mutations leading to telomeropathies are located at the TERT-TER and TEN-TRAP-TPP1 interfaces, highlighting the importance of TER-TERT and TPP1 interactions for telomerase activity, recruitment and as drug targets.
リンク	Nature / PubMed:35418675 / PubMed Central
手法	EM (単粒子)
解像度	3.3 - 4.3 Å
構造データ	26085 7trc EMDB-26085, PDB-7trc: Human telomerase H/ACA RNP at 3.3 Angstrom 手法: EM (単粒子) / 解像度: 3.3 Å 26086 7trd EMDB-26086, PDB-7trd: Human telomerase catalytic core structure at 3.3 Angstrom 手法: EM (単粒子) / 解像度: 3.3 Å 26087 7tre EMDB-26087, PDB-7tre: Human telomerase catalytic core with shelterin protein TPP1 手法: EM (単粒子) / 解像度: 3.5 Å 26088 7trf EMDB-26088, PDB-7trf: Human telomerase catalytic core RNP with H2A/H2B 手法: EM (単粒子) / 解像度: 3.7 Å EMDB-26090: Human telomerase catalytic core with TPP1-OB, P2a state1-1 手法: EM (単粒子) / 解像度: 4.2 Å EMDB-26091: Human telomerase catalytic core with TPP1-OB, P2a state 1-2 手法: EM (単粒子) / 解像度: 4.1 Å EMDB-26092: Human telomerase catalytic core with TPP1-OB, P2a state1-3 手法: EM (単粒子) / 解像度: 4.1 Å EMDB-26093: Human telomerase catalytic core with TPP1-OB, P2a state2 手法: EM (単粒子) / 解像度: 4.0 Å EMDB-26094: Human telomerase catalytic core without TPP1-OB, P2a state1 手法: EM (単粒子) / 解像度: 4.3 Å EMDB-26095: Human telomerase catalytic core without TPP1-OB, P2a state2 手法: EM (単粒子) / 解像度: 4.1 Å EMDB-26096: Human telomerase catalytic core without TPP1 手法: EM (単粒子) / 解像度: 3.7 Å
由来	homo sapiens (ヒト)
キーワード	REPLICATION / DNA / RNA