title: The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome.
abstract: Initiation of translation is the process by which initiator tRNA and the start codon of mRNA are positioned in the ribosomal P site. In eukaryotes, one of the first steps involves the binding of two small factors, eIF1 and eIF1A, to the small (40S) ribosomal subunit. This facilitates tRNA binding, allows scanning of mRNA, and maintains fidelity of start codon recognition. Using cryo-EM, we have obtained 3D reconstructions of 40S bound to both eIF1 and eIF1A, and with each factor alone. These structures reveal that together, eIF1 and eIF1A stabilize a conformational change that opens the mRNA binding channel. Biochemical data reveal that both factors accelerate the rate of ternary complex (eIF2*GTP*Met-tRNA(i)(Met)) binding to 40S but only eIF1A stabilizes this interaction. Our results suggest that eIF1 and eIF1A promote an open, scanning-competent preinitiation complex that closes upon start codon recognition and eIF1 release to stabilize ternary complex binding and clamp down on mRNA.
authors: MRC-Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
authors: Lori A
authors: LA
authors: Passmore
authors: T Martin
authors: TM
authors: Schmeing
authors: David
authors: D
authors: Maag
authors: Drew J
authors: DJ
authors: Applefield
authors: Michael G
authors: MG
authors: Acker
authors: Mikkel A
authors: MA
authors: Algire
authors: Jon R
authors: JR
authors: Lorsch
authors: V
authors: V
authors: Ramakrishnan
mesh_terms: D001665:Binding Sites; D020285:Cryoelectron Microscopy; D015977:Eukaryotic Initiation Factor-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D008968:Molecular Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry; D012335:RNA, Ribosomal / Q000737:chemistry; D012269:Ribosomal Proteins / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D015977:Eukaryotic Initiation Factor-1; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C026022:eukaryotic peptide initiation factor-1A