positive regulation of ubiquitin-protein transferase activity / negative regulation of RNA splicing / neural crest cell differentiation / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Ribosomal scanning and start codon recognition / laminin receptor activity ...positive regulation of ubiquitin-protein transferase activity / negative regulation of RNA splicing / neural crest cell differentiation / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Ribosomal scanning and start codon recognition / laminin receptor activity / Translation initiation complex formation / fibroblast growth factor binding / Protein hydroxylation / SARS-CoV-1 modulates host translation machinery / TOR signaling / mTORC1-mediated signalling / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / cellular response to ethanol / Eukaryotic Translation Termination / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / Viral mRNA Translation / ubiquitin ligase inhibitor activity / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of ubiquitin-dependent protein catabolic process / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / rough endoplasmic reticulum / positive regulation of cell cycle / laminin binding / translation initiation factor binding / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / cytosolic ribosome / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / antiviral innate immune response / Resolution of Sister Chromatid Cohesion / stress granule assembly / erythrocyte differentiation / positive regulation of translation / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / innate immune response in mucosa / maturation of SSU-rRNA / mRNA 3'-UTR binding / neural tube closure / small-subunit processome / translational initiation / RHO GTPases Activate Formins / response to insulin / maintenance of translational fidelity / modification-dependent protein catabolic process / GABA-ergic synapse / mRNA 5'-UTR binding / response to virus / Regulation of expression of SLITs and ROBOs / RMTs methylate histone arginines / protein tag activity / cytoplasmic ribonucleoprotein granule / rRNA processing / Separation of Sister Chromatids / antimicrobial humoral immune response mediated by antimicrobial peptide / glucose homeostasis / antibacterial humoral response / ribosomal small subunit assembly / presynapse / virus receptor activity / protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / ribosome binding / ribosomal small subunit biogenesis / 5'-3' RNA helicase activity / 付加脱離酵素(リアーゼ); P-Oリアーゼ類; - / cell body / small ribosomal subunit / small ribosomal subunit rRNA binding / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / cytosolic small ribosomal subunit / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / TRAF3-dependent IRF activation pathway / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / snRNP Assembly / Translation of Replicase and Assembly of the Replication Transcription Complex / Replication of the SARS-CoV-2 genome / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エキソリボヌクレアーゼ / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase / host cell endoplasmic reticulum-Golgi intermediate compartment / host cell endosome / 3'-5'-RNA exonuclease activity 類似検索 - 分子機能
40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. ...40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / : / 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 S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / Ribosomal protein S30 / Ribosomal protein S30 / : / Ribosomal protein S7e signature. / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / Ribosomal protein S8e, conserved site / Ribosomal protein S8e signature. / Ribosomal protein S27e signature. / Ribosomal protein S6, eukaryotic / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily / Ribosomal S17 / 40S ribosomal protein S1/3, eukaryotes / 40S ribosomal protein S11, N-terminal / Ribosomal_S17 N-terminal / Ribosomal protein S7e / Ribosomal protein S7e / : / Ribosomal S24e conserved site / Ribosomal protein S24e signature. / Ribosomal protein S4e, N-terminal / RS4NT (NUC023) domain / Ribosomal protein S4, KOW domain / Ribosomal protein S4e / Ribosomal protein S4e, central region / Ribosomal protein S4e, central domain superfamily / Ribosomal family S4e / Ribosomal protein S6/S6e/A/B/2, conserved site / Ribosomal protein S17, archaeal/eukaryotic / Ribosomal protein S6e signature. / Ribosomal protein S23, eukaryotic/archaeal / Ribosomal protein S24e / Ribosomal protein S24e / Ribosomal protein S8e / Ribosomal protein S27 / Ribosomal protein S27, zinc-binding domain superfamily / Ribosomal protein S27 / Ribosomal protein S3Ae / Ribosomal S3Ae family / Ribosomal S3Ae family / Ribosomal protein S6e / Ribosomal protein S6e / Ribosomal protein S6e / Ribosomal protein S13/S15, N-terminal / Ribosomal protein S15P / Ribosomal S13/S15 N-terminal domain / Ribosomal S13/S15 N-terminal domain / Ribosomal protein S4/S9, eukaryotic/archaeal / Ribosomal protein S8e/ribosomal biogenesis NSA2 / Ribosomal protein S8e / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ribosomal protein S2 signature 2. / Ribosomal protein S2 signature 1. / Ribosomal protein S5, N-terminal, conserved site / Ribosomal protein S5 signature. / Ubiquitin family / Ribosomal protein S2, conserved site / : / Ribosomal protein S2 / Ribosomal protein S2, flavodoxin-like domain superfamily / Ribosomal protein S2 / Ribosomal protein S17, conserved site / Ribosomal protein S17 signature. / Ribosomal protein S5 / S5 double stranded RNA-binding domain profile. / Ribosomal protein S5, N-terminal / Ribosomal protein S5, C-terminal / Ribosomal protein S5, N-terminal domain / Ribosomal protein S5, C-terminal domain / Ribosomal protein S4/S9 N-terminal domain / Ribosomal protein S8 signature. 類似検索 - ドメイン・相同性
Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Replicase polyprotein 1ab / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 ...Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Replicase polyprotein 1ab / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Small ribosomal subunit protein eS4, X isoform / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS26 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Small ribosomal subunit protein eS32 / Small ribosomal subunit protein eS21 類似検索 - 構成要素
生物種
Homo sapiens (ヒト) / Severe acute respiratory syndrome coronavirus 2 (ウイルス)
ジャーナル: Nat Struct Mol Biol / 年: 2020 タイトル: SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. 著者: Katharina Schubert / Evangelos D Karousis / Ahmad Jomaa / Alain Scaiola / Blanca Echeverria / Lukas-Adrian Gurzeler / Marc Leibundgut / Volker Thiel / Oliver Mühlemann / Nenad Ban / 要旨: The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show ...The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5' untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes.