The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome

Lori A. Passmore, T. Martin Schmeing, David Maag, Drew J. Applefield, Michael G. Acker, Mikkel A Algire, Jon R. Lorsch, V. Ramakrishnan

Research output: Contribution to journalArticle

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-tRNAi 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.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalMolecular Cell
Volume26
Issue number1
DOIs
StatePublished - Apr 13 2007

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Eukaryotic Initiation Factors
Ribosomes
Initiator Codon
Messenger RNA
Eukaryotic Small Ribosome Subunits
Small Ribosome Subunits
RNA, Transfer, Met
Transfer RNA
Eukaryota

Keywords

  • RNA

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Passmore, L. A., Schmeing, T. M., Maag, D., Applefield, D. J., Acker, M. G., Algire, MA., ... Ramakrishnan, V. (2007). The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome. Molecular Cell, 26(1), 41-50. https://doi.org/10.1016/j.molcel.2007.03.018

The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome. / Passmore, Lori A.; Schmeing, T. Martin; Maag, David; Applefield, Drew J.; Acker, Michael G.; Algire, Mikkel A; Lorsch, Jon R.; Ramakrishnan, V.

In: Molecular Cell, Vol. 26, No. 1, 13.04.2007, p. 41-50.

Research output: Contribution to journalArticle

Passmore, LA, Schmeing, TM, Maag, D, Applefield, DJ, Acker, MG, Algire, MA, Lorsch, JR & Ramakrishnan, V 2007, 'The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome', Molecular Cell, vol. 26, no. 1, pp. 41-50. https://doi.org/10.1016/j.molcel.2007.03.018
Passmore, Lori A. ; Schmeing, T. Martin ; Maag, David ; Applefield, Drew J. ; Acker, Michael G. ; Algire, Mikkel A ; Lorsch, Jon R. ; Ramakrishnan, V. / The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome. In: Molecular Cell. 2007 ; Vol. 26, No. 1. pp. 41-50.
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