- EMDB-12632: Mammalian pre-termination 80S ribosome with eRF1 and eRF3 bound b... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-12632
タイトル
Mammalian pre-termination 80S ribosome with eRF1 and eRF3 bound by Blasticidin S.
マップデータ
試料
複合体: Mammalian pre-termination 80S ribosome with eRF1 and eRF3 bound by Blasticidin S.
タンパク質・ペプチド: x 79種
RNA: x 5種
リガンド: x 4種
キーワード
Inhibitor 80S Termination Complex Blasticidin S Translation NMD / RIBOSOME
機能・相同性
機能・相同性情報
Protein hydroxylation / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Translation initiation complex formation / Formation of the ternary complex, and subsequently, the 43S complex ...Protein hydroxylation / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Translation initiation complex formation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / translation termination factor activity / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Downregulation of ERBB4 signaling / Spry regulation of FGF signaling / Downregulation of ERBB2:ERBB3 signaling / NOD1/2 Signaling Pathway / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / EGFR downregulation / TCF dependent signaling in response to WNT / NRIF signals cell death from the nucleus / p75NTR recruits signalling complexes / NF-kB is activated and signals survival / Activated NOTCH1 Transmits Signal to the Nucleus / Downregulation of TGF-beta receptor signaling / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / Downregulation of SMAD2/3:SMAD4 transcriptional activity / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Senescence-Associated Secretory Phenotype (SASP) / Regulation of innate immune responses to cytosolic DNA / activated TAK1 mediates p38 MAPK activation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Regulation of FZD by ubiquitination / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Regulation of TNFR1 signaling / TNFR1-induced NF-kappa-B signaling pathway / Translesion synthesis by POLK / Translesion synthesis by POLI / Regulation of necroptotic cell death / HDR through Homologous Recombination (HRR) / Josephin domain DUBs / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / Processing of DNA double-strand break ends / Gap-filling DNA repair synthesis and ligation in GG-NER / Dual Incision in GG-NER / Fanconi Anemia Pathway / Regulation of TP53 Activity through Phosphorylation / Regulation of TP53 Degradation / Regulation of TP53 Activity through Methylation / Negative regulation of MET activity / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Downregulation of ERBB2 signaling / E3 ubiquitin ligases ubiquitinate target proteins / Regulation of PTEN localization / ER Quality Control Compartment (ERQC) / Regulation of expression of SLITs and ROBOs / Interferon alpha/beta signaling / Endosomal Sorting Complex Required For Transport (ESCRT) / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / IKK complex recruitment mediated by RIP1 / IRAK2 mediated activation of TAK1 complex / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Alpha-protein kinase 1 signaling pathway / RAS processing / Pexophagy / Negative regulation of FLT3 / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Regulation of NF-kappa B signaling / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Regulation of pyruvate metabolism / SCF-beta-TrCP mediated degradation of Emi1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Ovarian tumor domain proteases / Cyclin D associated events in G1 / Regulation of BACH1 activity / Negative regulation of FGFR1 signaling / Negative regulation of FGFR2 signaling / Negative regulation of FGFR3 signaling / Negative regulation of FGFR4 signaling / Negative regulation of MAPK pathway / Formation of Incision Complex in GG-NER / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Inactivation of CSF3 (G-CSF) signaling / Termination of translesion DNA synthesis / Iron uptake and transport / Negative regulators of DDX58/IFIH1 signaling / Deactivation of the beta-catenin transactivating complex / Metalloprotease DUBs / Major pathway of rRNA processing in the nucleolus and cytosol / GTP hydrolysis and joining of the 60S ribosomal subunit / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A 類似検索 - 分子機能
Peptide chain release factor eRF1/aRF1 / eRF1, domain 1 / eRF1 domain 2 / eRF1 domain 2 / eRF1 domain 1/Pelota-like / eRF1 domain 3 / eRF1, domain 2 superfamily / eRF1 domain 1 / eRF1 domain 3 / eRF1_1 ...Peptide chain release factor eRF1/aRF1 / eRF1, domain 1 / eRF1 domain 2 / eRF1 domain 2 / eRF1 domain 1/Pelota-like / eRF1 domain 3 / eRF1, domain 2 superfamily / eRF1 domain 1 / eRF1 domain 3 / eRF1_1 / 60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / : / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / 50S ribosomal protein L10, insertion domain superfamily / Ribosomal protein L23 / Ribosomal L28e/Mak16 / 60S ribosomal protein L10P, insertion domain / Ribosomal L28e protein family / Insertion domain in 60S ribosomal protein L10P / metallochaperone-like domain / TRASH domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Small (40S) ribosomal subunit Asc1/RACK1 / S27a-like superfamily / 40S Ribosomal protein S10 / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L10e / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L19, eukaryotic / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein S27a / : / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein L6e signature. / Ribosomal protein L30e signature 1. / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein L23/L25, N-terminal / Ribosomal protein L23, N-terminal domain / Ribosomal protein S3, eukaryotic/archaeal / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal protein L30e signature 2. / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L30e, conserved site / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / Ribosomal protein L35Ae, conserved site / Ribosomal protein L35Ae signature. / : / Ribosomal protein S19A/S15e / Ribosomal protein L34Ae / Ribosomal protein L34e / 60S ribosomal protein L19 / Ribosomal Protein L6, KOW domain / Ribosomal protein L30/YlxQ 類似検索 - ドメイン・相同性
Large ribosomal subunit protein eL24 / Small ribosomal subunit protein eS32 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein eL20 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein RACK1 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 ...Large ribosomal subunit protein eL24 / Small ribosomal subunit protein eS32 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein eL20 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein RACK1 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL10 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS12 / Large ribosomal subunit protein eL15 / Small ribosomal subunit protein uS11 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Small ribosomal subunit protein eS25 / Large ribosomal subunit protein eL30 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS28 / Large ribosomal subunit protein uL3 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein uS13 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein eL27 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein eL28 / Large ribosomal subunit protein eL34 / Eukaryotic peptide chain release factor subunit 1 / Ubiquitin-ribosomal protein eS31 fusion protein / Small ribosomal subunit protein eS21 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein eL19 / Small ribosomal subunit protein eS17 / 40S ribosomal protein S26 / Large ribosomal subunit protein eL37 類似検索 - 構成要素
ジャーナル: Nucleic Acids Res / 年: 2021 タイトル: Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA. 著者: Kyle T Powers / Flint Stevenson-Jones / Sathish K N Yadav / Beate Amthor / Joshua C Bufton / Ufuk Borucu / Dakang Shen / Jonas P Becker / Daria Lavysh / Matthias W Hentze / Andreas E Kulozik ...著者: Kyle T Powers / Flint Stevenson-Jones / Sathish K N Yadav / Beate Amthor / Joshua C Bufton / Ufuk Borucu / Dakang Shen / Jonas P Becker / Daria Lavysh / Matthias W Hentze / Andreas E Kulozik / Gabriele Neu-Yilik / Christiane Schaffitzel / 要旨: Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding ...Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3'CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor 1 (eRF1), it interferes with eRF1's accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production.