negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / regulation of translational initiation / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity ...negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / regulation of translational initiation / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / protein-synthesizing GTPase / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / positive regulation of DNA-templated transcription initiation / TNFR1-mediated ceramide production / negative regulation of RNA splicing / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / protein kinase A binding / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / pigmentation / positive regulation of mitochondrial depolarization / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / TOR signaling / positive regulation of GTPase activity / iron-sulfur cluster binding / mTORC1-mediated signalling / Peptide chain elongation / regulation of cell division / 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 / negative regulation of protein binding / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / ubiquitin ligase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / 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) / positive regulation of signal transduction by p53 class mediator / 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 / regulation of translational fidelity / positive regulation of microtubule polymerization / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / positive regulation of intrinsic apoptotic signaling pathway / spindle assembly / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / translation regulator activity / 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 / ribosomal small subunit export from nucleus / positive regulation of cell cycle / translation initiation factor binding / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / translation initiation factor activity / Maturation of protein E / gastrulation / DNA-(apurinic or apyrimidinic site) endonuclease activity / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / IRAK2 mediated activation of TAK1 complex / Prevention of phagosomal-lysosomal fusion / Alpha-protein kinase 1 signaling pathway / signaling adaptor activity / Glycogen synthesis Similarity search - Function
Elongation factor Tu-type domain / Elongation factor Tu domain 4 / Translation initiation factor IF- 2, domain 3 / Translation-initiation factor 2 / Translation initiation factor IF- 2 / Translation initiation factor IF-2, domain 3 superfamily / : / Ribosomal protein S26e signature. / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. ...Elongation factor Tu-type domain / Elongation factor Tu domain 4 / Translation initiation factor IF- 2, domain 3 / Translation-initiation factor 2 / Translation initiation factor IF- 2 / Translation initiation factor IF-2, domain 3 superfamily / : / Ribosomal protein S26e signature. / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / S27a-like superfamily / 40S Ribosomal protein S10 / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S27a / : / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S7e signature. / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S3, eukaryotic/archaeal / 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 S19A/S15e / Ribosomal protein S27e signature. / Ribosomal protein S6, eukaryotic / Ribosomal protein S19e / Ribosomal protein S19e / Ribosomal_S19e / 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 / Translational (tr)-type GTP-binding domain / Elongation factor Tu GTP binding domain / Translational (tr)-type guanine nucleotide-binding (G) domain profile. / 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 S6e / Ribosomal protein S6e / Ribosomal protein S5/S7, eukaryotic/archaeal / Ribosomal protein S6e / 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 S3, conserved site / Ribosomal protein S3 signature. / : / KH domain / Type-2 KH domain profile. / K Homology domain, type 2 / Ribosomal protein S3, C-terminal / Ribosomal protein S3, C-terminal domain / Ribosomal protein S3, C-terminal domain superfamily / Small GTP-binding protein domain / Ribosomal protein S15/S19, conserved site / Ribosomal protein S19 signature. / Ribosomal protein S19/S15 / Ribosomal protein S19/S15, superfamily / Ribosomal protein S19 / Ribosomal protein S5, N-terminal, conserved site / Ribosomal protein S5 signature. / Ribosomal protein S7, conserved site / Ubiquitin family Similarity search - Domain/homology
Small ribosomal subunit protein eS10 / Eukaryotic translation initiation factor 5B / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 ...Small ribosomal subunit protein eS10 / Eukaryotic translation initiation factor 5B / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS17 / Small ribosomal subunit protein eS4, X isoform / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS26 / Ubiquitin-ribosomal protein eS31 fusion protein / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.2 Å
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)
(GM011378
United States
Citation
Journal: Nature / Year: 2022 Title: eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining. Authors: Christopher P Lapointe / Rosslyn Grosely / Masaaki Sokabe / Carlos Alvarado / Jinfan Wang / Elizabeth Montabana / Nancy Villa / Byung-Sik Shin / Thomas E Dever / Christopher S Fraser / ...Authors: Christopher P Lapointe / Rosslyn Grosely / Masaaki Sokabe / Carlos Alvarado / Jinfan Wang / Elizabeth Montabana / Nancy Villa / Byung-Sik Shin / Thomas E Dever / Christopher S Fraser / Israel S Fernández / Joseph D Puglisi / Abstract: Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases. A key commitment step is when the ribosomal subunits join at a ...Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases. A key commitment step is when the ribosomal subunits join at a translation start site on a messenger RNA to form a functional ribosome. Here, we combined single-molecule spectroscopy and structural methods using an in vitro reconstituted system to examine how the human ribosomal subunits join. Single-molecule fluorescence revealed when the universally conserved eukaryotic initiation factors eIF1A and eIF5B associate with and depart from initiation complexes. Guided by single-molecule dynamics, we visualized initiation complexes that contained both eIF1A and eIF5B using single-particle cryo-electron microscopy. The resulting structure revealed how eukaryote-specific contacts between the two proteins remodel the initiation complex to orient the initiator aminoacyl-tRNA in a conformation compatible with ribosomal subunit joining. Collectively, our findings provide a quantitative and architectural framework for the molecular choreography orchestrated by eIF1A and eIF5B during translation initiation in humans.
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