A conformational change in the eukaryotic translation preinitiation complex and release of eIF1 signal recognition of the start codon

David Maag, Christie A. Fekete, Zygmunt Gryczynski, Jon R. Lorsch

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

During eukaryotic translation initiation, ribosomal 43S complexes scan mRNAs for the correct AUG codon at which to begin translation. Start codon recognition triggers GTP hydrolysis, committing the complex to engagement at that point on the mRNA. While fidelity at this step is essential, the nature of the codon recognition event and the mechanism by which it activates GTP hydrolysis are poorly understood. Here we report the changes that occur within the 43S·mRNA complex in response to AUG codon recognition. eIF1 and eIF1A are key players in assembly of 43S·mRNA complexes capable of locating initiation codons. We observed FRET between these two factors when bound to the 40S subunit. Using steady-state FRET, anisotropy, and kinetic analyses, we demonstrate that start codon recognition results in a conformational change and release of eIF1 from the ribosome. These rearrangements probably play a role in triggering GTP hydrolysis and committing the complex to downstream events.

Original languageEnglish
Pages (from-to)265-275
Number of pages11
JournalMolecular Cell
Volume17
Issue number2
DOIs
StatePublished - 21 Jan 2005

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Initiator Codon
Guanosine Triphosphate
Codon
Hydrolysis
Messenger RNA
Anisotropy
Ribosomes

Cite this

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abstract = "During eukaryotic translation initiation, ribosomal 43S complexes scan mRNAs for the correct AUG codon at which to begin translation. Start codon recognition triggers GTP hydrolysis, committing the complex to engagement at that point on the mRNA. While fidelity at this step is essential, the nature of the codon recognition event and the mechanism by which it activates GTP hydrolysis are poorly understood. Here we report the changes that occur within the 43S·mRNA complex in response to AUG codon recognition. eIF1 and eIF1A are key players in assembly of 43S·mRNA complexes capable of locating initiation codons. We observed FRET between these two factors when bound to the 40S subunit. Using steady-state FRET, anisotropy, and kinetic analyses, we demonstrate that start codon recognition results in a conformational change and release of eIF1 from the ribosome. These rearrangements probably play a role in triggering GTP hydrolysis and committing the complex to downstream events.",
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A conformational change in the eukaryotic translation preinitiation complex and release of eIF1 signal recognition of the start codon. / Maag, David; Fekete, Christie A.; Gryczynski, Zygmunt; Lorsch, Jon R.

In: Molecular Cell, Vol. 17, No. 2, 21.01.2005, p. 265-275.

Research output: Contribution to journalArticle

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