eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining

Article

关键词: X-RAY STRUCTURES;    TRANSLATION INITIATION;    PROTEIN-SYNTHESIS;    TERNARY COMPLEX;    FACTORS 1A;    BINDING;    CODON;    5B;    RECOGNITION;    EUKARYOTES;   

DOI  :  10.1038/s41586-022-04858-z

来源: SCIE

【 摘 要 】

Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases(1,)(2). 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 fort he molecular choreography orchestrated by eIF1A and eIF5B during translation initiation in humans.

【 授权许可】

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