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基本情報
登録情報 | ![]() | ||||||||||||
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タイトル | Human telomerase H/ACA RNP at 3.3 Angstrom | ||||||||||||
![]() | H/ACA lobe of human telomerase | ||||||||||||
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![]() | DNA / RNA / REPLICATION | ||||||||||||
機能・相同性 | ![]() telomere formation via telomerase / box H/ACA scaRNP complex / box H/ACA telomerase RNP complex / telomerase RNA localization to Cajal body / protein localization to Cajal body / snoRNA guided rRNA pseudouridine synthesis / box H/ACA snoRNP complex / 異性化酵素; 分子内転位酵素; ムターゼ; その他の基を移すもの / rRNA pseudouridine synthesis / box H/ACA sno(s)RNA 3'-end processing ...telomere formation via telomerase / box H/ACA scaRNP complex / box H/ACA telomerase RNP complex / telomerase RNA localization to Cajal body / protein localization to Cajal body / snoRNA guided rRNA pseudouridine synthesis / box H/ACA snoRNP complex / 異性化酵素; 分子内転位酵素; ムターゼ; その他の基を移すもの / rRNA pseudouridine synthesis / box H/ACA sno(s)RNA 3'-end processing / pseudouridine synthesis / snRNA pseudouridine synthesis / enzyme-directed rRNA pseudouridine synthesis / telomerase RNA stabilization / Cajal body organization / box H/ACA snoRNA binding / telomerase activity / regulation of telomerase RNA localization to Cajal body / mRNA pseudouridine synthesis / pseudouridine synthase activity / scaRNA localization to Cajal body / positive regulation of establishment of protein localization to telomere / positive regulation of protein localization to Cajal body / positive regulation of telomerase RNA localization to Cajal body / sno(s)RNA-containing ribonucleoprotein complex / Telomere Extension By Telomerase / telomerase holoenzyme complex / telomerase RNA binding / rRNA modification in the nucleus and cytosol / positive regulation of double-strand break repair / Cajal body / positive regulation of double-strand break repair via nonhomologous end joining / Association of TriC/CCT with target proteins during biosynthesis / : / RNA folding / telomere maintenance via telomerase / positive regulation of double-strand break repair via homologous recombination / positive regulation of DNA repair / RNA processing / positive regulation of telomere maintenance via telomerase / fibrillar center / rRNA processing / site of double-strand break / protein-folding chaperone binding / histone binding / chromosome, telomeric region / nuclear body / DNA repair / ubiquitin protein ligase binding / protein-containing complex binding / nucleolus / RNA binding / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | ||||||||||||
![]() | Liu B / He Y | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of active human telomerase with telomere shelterin protein TPP1. 著者: Baocheng Liu / Yao He / Yaqiang Wang / He Song / Z Hong Zhou / Juli Feigon / ![]() 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. | ||||||||||||
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マップデータ | ![]() | 116.5 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.2 KB 16.2 KB | 表示 表示 | ![]() |
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「今月の分子」の関連する項目 |
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注釈 | H/ACA lobe of human telomerase | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.1 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
-全体 : human telomerase H/ACA RNP
全体 | 名称: human telomerase H/ACA RNP |
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要素 |
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-超分子 #1: human telomerase H/ACA RNP
超分子 | 名称: human telomerase H/ACA RNP / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Telomerase Cajal body protein 1
分子 | 名称: Telomerase Cajal body protein 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 59.35707 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKTLETQPLA PDCCPSDQDP APAHPSPHAS PMNKNADSEL MPPPPERGDP PRLSPDPVAG SAVSQELREG DPVSLSTPLE TEFGSPSEL SPRIEEQELS ENTSLPAEEA NGSLSEEEAN GPELGSGKAM EDTSGEPAAE DEGDTAWNYS FSQLPRFLSG S WSEFSTQP ...文字列: MKTLETQPLA PDCCPSDQDP APAHPSPHAS PMNKNADSEL MPPPPERGDP PRLSPDPVAG SAVSQELREG DPVSLSTPLE TEFGSPSEL SPRIEEQELS ENTSLPAEEA NGSLSEEEAN GPELGSGKAM EDTSGEPAAE DEGDTAWNYS FSQLPRFLSG S WSEFSTQP ENFLKGCKWA PDGSCILTNS ADNILRIYNL PPELYHEGEQ VEYAEMVPVL RMVEGDTIYD YCWYSLMSSA QP DTSYVAS SSRENPIHIW DAFTGELRAS FRAYNHLDEL TAAHSLCFSP DGSQLFCGFN RTVRVFSTAR PGRDCEVRAT FAK KQGQSG IISCIAFSPA QPLYACGSYG RSLGLYAWDD GSPLALLGGH QGGITHLCFH PDGNRFFSGA RKDAELLCWD LRQS GYPLW SLGREVTTNQ RIYFDLDPTG QFLVSGSTSG AVSVWDTDGP GNDGKPEPVL SFLPQKDCTN GVSLHPSLPL LATAS GQRV FPEPTESGDE GEELGLPLLS TRHVHLECRL QLWWCGGAPD SSIPDDHQGE KGQGGTEGGV GELI UniProtKB: Telomerase Cajal body protein 1 |
-分子 #2: H/ACA ribonucleoprotein complex subunit DKC1
分子 | 名称: H/ACA ribonucleoprotein complex subunit DKC1 / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO EC番号: 異性化酵素; 分子内転位酵素; ムターゼ; その他の基を移すもの |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 57.779211 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MADAEVIILP KKHKKKKERK SLPEEDVAEI QHAEEFLIKP ESKVAKLDTS QWPLLLKNFD KLNVRTTHYT PLACGSNPLK REIGDYIRT GFINLDKPSN PSSHEVVAWI RRILRVEKTG HSGTLDPKVT GCLIVCIERA TRLVKSQQSA GKEYVGIVRL H NAIEGGTQ ...文字列: MADAEVIILP KKHKKKKERK SLPEEDVAEI QHAEEFLIKP ESKVAKLDTS QWPLLLKNFD KLNVRTTHYT PLACGSNPLK REIGDYIRT GFINLDKPSN PSSHEVVAWI RRILRVEKTG HSGTLDPKVT GCLIVCIERA TRLVKSQQSA GKEYVGIVRL H NAIEGGTQ LSRALETLTG ALFQRPPLIA AVKRQLRVRT IYESKMIEYD PERRLGIFWV SCEAGTYIRT LCVHLGLLLG VG GQMQELR RVRSGVMSEK DHMVTMHDVL DAQWLYDNHK DESYLRRVVY PLEKLLTSHK RLVMKDSAVN AICYGAKIML PGV LRYEDG IEVNQEIVVI TTKGEAICMA IALMTTAVIS TCDHGIVAKI KRVIMERDTY PRKWGLGPKA SQKKLMIKQG LLDK HGKPT DSTPATWKQE YVDYSESAKK EVVAEVVKAP QVVAEAAKTA KRKRESESES DETPPAAPQL IKKEKKKSKK DKKAK AGLE SGAEPGDGDS DTTKKKKKKK KAKEVELVSE UniProtKB: H/ACA ribonucleoprotein complex subunit DKC1 |
-分子 #3: H/ACA ribonucleoprotein complex subunit 3
分子 | 名称: H/ACA ribonucleoprotein complex subunit 3 / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.719989 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MFLQYYLNEQ GDRVYTLKKF DPMGQQTCSA HPARFSPDDK YSRHRITIKK RFKVLMTQQP RPVL UniProtKB: H/ACA ribonucleoprotein complex subunit 3 |
-分子 #5: H/ACA ribonucleoprotein complex subunit 1
分子 | 名称: H/ACA ribonucleoprotein complex subunit 1 / タイプ: protein_or_peptide / ID: 5 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 22.387963 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSFRGGGRGG FNRGGGGGGF NRGGSSNHFR GGGGGGGGGN FRGGGRGGFG RGGGRGGFNK GQDQGPPERV VLLGEFLHPC EDDIVCKCT TDENKVPYFN APVYLENKEQ IGKVDEIFGQ LRDFYFSVKL SENMKASSFK KLQKFYIDPY KLLPLQRFLP R PPGEKGPP ...文字列: MSFRGGGRGG FNRGGGGGGF NRGGSSNHFR GGGGGGGGGN FRGGGRGGFG RGGGRGGFNK GQDQGPPERV VLLGEFLHPC EDDIVCKCT TDENKVPYFN APVYLENKEQ IGKVDEIFGQ LRDFYFSVKL SENMKASSFK KLQKFYIDPY KLLPLQRFLP R PPGEKGPP RGGGRGGRGG GRGGGGRGGG RGGGFRGGRG GGGGGFRGGR GGGFRGRGH UniProtKB: H/ACA ribonucleoprotein complex subunit 1 |
-分子 #6: H/ACA ribonucleoprotein complex subunit 2
分子 | 名称: H/ACA ribonucleoprotein complex subunit 2 / タイプ: protein_or_peptide / ID: 6 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 17.22607 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MTKIKADPDG PEAQAEACSG ERTYQELLVN QNPIAQPLAS RRLTRKLYKC IKKAVKQKQI RRGVKEVQKF VNKGEKGIMV LAGDTLPIE VYCHLPVMCE DRNLPYVYIP SKTDLGAAAG SKRPTCVIMV KPHEEYQEAY DECLEEVQSL PLPL UniProtKB: H/ACA ribonucleoprotein complex subunit 2 |
-分子 #4: Telomerase RNA, partial sequence
分子 | 名称: Telomerase RNA, partial sequence / タイプ: rna / ID: 4 / コピー数: 1 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 145.477797 KDa |
配列 | 文字列: GGGUUGCGGA GGGUGGGCCU GGGAGGGGUG GUGGCCAUUU UUUGUCUAAC CCUAACUGAG AAGGGCGUAG GCGCCGUGCU UUUGCUCCC CGCGCGCUGU UUUUCUCGCU GACUUUCAGC GGGCGGAAAA GCCUCGGCCU GCCGCCUUCC ACCGUUCAUU C UAGAGCAA ...文字列: GGGUUGCGGA GGGUGGGCCU GGGAGGGGUG GUGGCCAUUU UUUGUCUAAC CCUAACUGAG AAGGGCGUAG GCGCCGUGCU UUUGCUCCC CGCGCGCUGU UUUUCUCGCU GACUUUCAGC GGGCGGAAAA GCCUCGGCCU GCCGCCUUCC ACCGUUCAUU C UAGAGCAA ACAAAAAAUG UCAGCUGCUG GCCCGUUCGC CCCUCCCGGG GACCUGCGGC GGGUCGCCUG CCCAGCCCCC GA ACCCCGC CUGGAGGCCG CGGUCGGCCC GGGGCUUCUC CGGAGGCACC CACUGCCACC GCGAAGAGUU GGGCUCUGUC AGC CGCGGG UCUCUCGGGG GCGAGGGCGA GGUUCAGGCC UUUCAGGCCG CAGGAAGAGG AACGGAGCGA GUCCCCGCGC GCGG CGCGA UUCCCUGAGC UGUGGGACGU GCACCCAGGA CUCGGCUCAC ACAUGC GENBANK: GENBANK: U85256.1 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 55.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 4.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: EMDB MAP EMDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 256859 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |