The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct to interacts to eIF1, eIF2, eIF3, and eIF4G

Yasufumi Yamamoto, Chingakham Ranjit Singh, Assen Marintchev, Nathan S. Hall, Ernest M. Hannig, Gerhard Wagner, Katsura Asano

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Eukaryotic translation initiation factor (eIF) 5 is crucial for the assembly of the eukaryotic preinitiation complex. This activity is mediated by the ability of its C-terminal HEAT domain to interact with eIF1, eIF2, and eIF3 in the multifactor complex and with eIF4G in the 48S complex. However, the binding sites for these factors on eIF5-C-terminal domain (CTD) have not been known. Here we present a homology model for eIF5-CTD based on the HEAT domain of eIF2Bε. We show that the binding site for eIF2β is located in a surface area containing aromatic and acidic residues (aromatic/acidic boxes), that the binding sites for eIF1 and eIF3c are located in a conserved surface region of basic residues, and that eIF4G binds eIF5-CTD at an interface overlapping with the acidic area. Mutations in these distinct eIF5 surface areas impair GCN4 translational control by disrupting preinitiation complex interactions. These results indicate that the eIF5 HEAT domain is a critical nucleation core for preinitiation complex assembly and function.

Original languageEnglish (US)
Pages (from-to)16164-16169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number45
DOIs
StatePublished - Nov 8 2005

All Science Journal Classification (ASJC) codes

  • General

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