{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lapointe CP"],"funding":["NIA NIH HHS","NIGMS NIH HHS","NIH HHS"],"pagination":["185-190"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9728550"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["607(7917)"],"pubmed_abstract":["Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases<sup>1,2</sup>. 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."],"journal":["Nature"],"pubmed_title":["eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining."],"pmcid":["PMC9728550"],"funding_grant_id":["R01 GM113078","R01 GM092927","K99 GM144678","RF1 AG064690","AG064690","R35 GM145306","R01 AG064690","R00 GM144678","R01 GM051266","GM011378"],"pubmed_authors":["Shin BS","Puglisi JD","Sokabe M","Lapointe CP","Montabana E","Villa N","Grosely R","Alvarado C","Dever TE","Fraser CS","Fernandez IS","Wang J"],"additional_accession":[]},"is_claimable":false,"name":"eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining.","description":"Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases<sup>1,2</sup>. 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-05-28T12:55:00.308Z","creation":"2025-02-18T22:34:41.531Z"},"accession":"S-EPMC9728550","cross_references":{"pubmed":["35732735"],"doi":["10.1038/s41586-022-04858-z"]}}