288 results found
    1. Structural Biology and Molecular Biophysics

    Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition

    Jose Luis Llácer et al.
    The N-terminal domain (NTD) of the initiation factor eIF5 bound to the 40S subunit at the precise location vacated by eIF1 promotes tRNAi accommodation at AUG codons.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski et al.
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Fail-safe control of translation initiation by dissociation of eIF2α phosphorylated ternary complexes

    Martin D Jennings et al.
    Phosphorylated translation initiation factor eIF2, a potent inhibitor of protein synthesis in eukaryotic cells, is also inhibitory to protein synthesis when bound to GTP and initiator tRNA broadening the reach and immediacy of eIF2-mediated control.
    1. Biochemistry and Chemical Biology

    Repression of ferritin light chain translation by human eIF3

    Mia C Pulos-Holmes et al.
    Human ferritin light chain (FTL) mRNA translation is regulated via its 5'-untranslated region (5'-UTR) by three mechanisms: RNA folding, iron response protein binding, and eukaryotic translation initiation factor eIF3 binding.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes

    Yao Liang Wong et al.
    Vanishing White Matter Disease mutations compromise the function of the essential translation initiation factor eIF2B by destabilizing the holoenzyme, and the small molecule ISRIB reverses their pathogenic effect by promoting complex formation.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Interface between 40S exit channel protein uS7/Rps5 and eIF2α modulates start codon recognition in vivo

    Jyothsna Visweswaraiah, Alan G Hinnebusch
    The small subunit ribosomal protein uS7/Rps5 interacts with translation initiation factor eIF2α to stabilize first the open, and then the closed conformation of the pre-initiation complex to promote accurate start codon selection in vivo.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Discovery of a small molecule that inhibits bacterial ribosome biogenesis

    Jonathan M Stokes et al.
    The anticonvulsant drug lamotrigine inhibits bacterial ribosome biogenesis and reveals an unexplored role for initiation factor 2 (IF2) in ribosome assembly.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    eIF2B activator prevents neurological defects caused by a chronic integrated stress response

    Yao Liang Wong et al.
    Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.
    1. Neuroscience

    Translational control of nicotine-evoked synaptic potentiation in mice and neuronal responses in human smokers by eIF2α

    Andon N Placzek et al.
    An evolutionarily conserved mechanism involving translational control by p-eIF2α underlies vulnerability to nicotine addiction.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Eukaryotic translation initiation factor 3 plays distinct roles at the mRNA entry and exit channels of the ribosomal preinitiation complex

    Colin Echeverría Aitken et al.
    Eukaryotic translation initiation factor 3 (eIF3) is required to stabilize the binding of mRNA at the exit channel of the small ribosomal subunit and acts at the entry channel to accelerate mRNA recruitment to the translation preinitiation complex.

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