cytoplasmic side of lysosomal membrane / regulation of D-erythro-sphingosine kinase activity / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / eukaryotic 80S initiation complex ...cytoplasmic side of lysosomal membrane / regulation of D-erythro-sphingosine kinase activity / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / eukaryotic 80S initiation complex / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / protein tyrosine kinase inhibitor activity / translation at presynapse / positive regulation of respiratory burst involved in inflammatory response / axial mesoderm development / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / negative regulation of formation of translation preinitiation complex / nucleolus organization / ribosomal protein import into nucleus / IRE1-RACK1-PP2A complex / : / exit from mitosis / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / 90S preribosome assembly / TNFR1-mediated ceramide production / laminin receptor activity / negative regulation of DNA repair / negative regulation of RNA splicing / optic nerve development / TORC2 complex binding / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / retinal ganglion cell axon guidance / middle ear morphogenesis / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / regulation of G1 to G0 transition / alpha-beta T cell differentiation / 顔料 / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein kinase A binding / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / translational elongation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / response to aldosterone / G1 to G0 transition / cortical actin cytoskeleton / homeostatic process / lung morphogenesis / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / regulation of cell division / ヒドロキシル化 / iron-sulfur cluster binding / macrophage chemotaxis / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / phagocytic cup / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / Viral mRNA Translation / protein-RNA complex assembly / protein localization to nucleus 類似検索 - 分子機能
Translation elongation factor EF1A, eukaryotic/archaeal / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 60s Acidic ribosomal protein / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Translation elongation factor EFTu/EF1A, C-terminal / Elongation factor Tu C-terminal domain / 60S acidic ribosomal protein P0 / Ribosomal protein L6, N-terminal domain ...Translation elongation factor EF1A, eukaryotic/archaeal / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 60s Acidic ribosomal protein / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Translation elongation factor EFTu/EF1A, C-terminal / Elongation factor Tu C-terminal domain / 60S acidic ribosomal protein P0 / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Ribosomal protein L23 / Ubiquitin-like protein FUBI / Translation elongation factor EF1A/initiation factor IF2gamma, C-terminal / Ribosomal protein L28e / Ribosomal protein L41 / Ribosomal L15/L27a, N-terminal / Ribosomal protein L41 / : / 50S ribosomal protein L10, insertion domain superfamily / metallochaperone-like domain / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / TRASH domain / Ribosomal protein S21e, conserved site / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S19e, conserved site / Ribosomal protein S26e / Ribosomal protein L29e / Ribosomal protein S26e signature. / Tr-type G domain, conserved site / Translational (tr)-type guanine nucleotide-binding (G) domain signature. / Ribosomal protein S2, eukaryotic / Ribosomal L29e protein family / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / : / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S21e signature. / Ribosomal protein S12e signature. / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein S12e / Ribosomal protein S19e / Ribosomal_S19e / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S8e, conserved site / : / Ribosomal protein L24e, conserved site / Ribosomal protein S4e, N-terminal, conserved site / 40S ribosomal protein S4, C-terminal domain / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S19e / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal protein L23/L25, N-terminal / Ribosomal L22e protein family / 40S ribosomal protein S4 C-terminus / Ribosomal protein S4e, N-terminal / Ribosomal protein L30e, conserved site / Ribosomal protein L34e, conserved site / 40S Ribosomal protein S10 / S27a-like superfamily / Ribosomal protein L23, N-terminal domain / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein S8e / Ribosomal protein S4, KOW domain / Ribosomal protein S4e / Ribosomal protein S4e, central region / Ribosomal protein L1, conserved site / Ribosomal protein S4e, central domain superfamily / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal Protein L6, KOW domain / Ribosomal protein L30/YlxQ / Ribosomal protein S25 / S25 ribosomal protein / RS4NT (NUC023) domain / Ribosomal protein L1 signature. / : / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein L1 / Ribosomal protein L14e domain / 60S ribosomal protein L6E / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein L34Ae / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein L27e, conserved site 類似検索 - ドメイン・相同性
Large ribosomal subunit protein eL42 / Large ribosomal subunit protein uL10 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 ...Large ribosomal subunit protein eL42 / Large ribosomal subunit protein uL10 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Small ribosomal subunit protein eS19 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Small ribosomal subunit protein eS27 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein eL37 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL8 / Small ribosomal subunit protein eS4, X isoform / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein eS6 / Large ribosomal subunit protein uL14 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein eS28 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein uL1 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Small ribosomal subunit protein eS32 / Ubiquitin-ribosomal protein eS31 fusion protein / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Elongation factor 1-alpha 1 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Large ribosomal subunit protein eL36 類似検索 - 構成要素
ジャーナル: Nature / 年: 2023 タイトル: mRNA decoding in human is kinetically and structurally distinct from bacteria. 著者: Mikael Holm / S Kundhavai Natchiar / Emily J Rundlet / Alexander G Myasnikov / Zoe L Watson / Roger B Altman / Hao-Yuan Wang / Jack Taunton / Scott C Blanchard / 要旨: In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives ...In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives principally from studies on bacterial systems. Although key features are conserved across evolution, eukaryotes achieve higher-fidelity mRNA decoding than bacteria. In human, changes in decoding fidelity are linked to ageing and disease and represent a potential point of therapeutic intervention in both viral and cancer treatment. Here we combine single-molecule imaging and cryogenic electron microscopy methods to examine the molecular basis of human ribosome fidelity to reveal that the decoding mechanism is both kinetically and structurally distinct from that of bacteria. Although decoding is globally analogous in both species, the reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower. These distinctions arise from eukaryote-specific structural elements in the human ribosome and in the elongation factor eukaryotic elongation factor 1A (eEF1A) that together coordinate faithful tRNA incorporation at each mRNA codon. The distinct nature and timing of conformational changes within the ribosome and eEF1A rationalize how increased decoding fidelity is achieved and potentially regulated in eukaryotic species.