Eukaryotic Translation Initiation Factor 5 Functions as a GTPase-activating Protein

Supratik Das, Rajarshi Ghosh, Umadas Maitra

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Eukaryotic translation initiation factor 5 (eIF5) forms a complex with eIF2 by interacting with the β subunit of eIF2. This interaction is essential for eIF5-promoted hydrolysis of GTP bound to the 40 S initiation complex. In this work, we show that in addition to the eIF2β-binding region at the C terminus of eIF5, the N-terminal region of eIF5 is also required for eIF5-dependent GTP hydrolysis. Like other GTPase-activating proteins, eIF5 contains an invariant arginine residue (Arg-15) at its N terminus that is essential for its function. Mutation of this arginine residue to alanine or even to conservative lysine caused a severe defect in the ability of eIF5 to promote GTP hydrolysis from the 40 S initiation complex, although the ability of these mutant proteins to bind to eIF2β remained unchanged. These mutants were also defective in overall protein synthesis as well as in their ability to support cell growth of a ΔTIF5 yeast strain. Additionally, alanine substitution mutagenesis of eIF5 defined Lys-33 and Lys-55 as also critical for eIF5 function in vitro and in vivo. The implications of these results in relation to other well characterized GAPs are discussed and provide additional evidence that eIF5 functions as a GTPase-activating protein.

Original languageEnglish (US)
Pages (from-to)6720-6726
Number of pages7
JournalJournal of Biological Chemistry
Issue number9
StatePublished - Mar 2 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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