title: Eukaryotic initiation factor (eIF) 1 carries two distinct eIF5-binding faces important for multifactor assembly and AUG selection.
abstract: Eukaryotic initiation factor (eIF) 1 is a small protein (12 kDa) governing fidelity in translation initiation. It is recruited to the 40 S subunit in a multifactor complex with Met-tRNA(i)(Met), eIF2, eIF3, and eIF5 and binds near the P-site. eIF1 release in response to start codon recognition is an important signal to produce an 80 S initiation complex. Although the ribosome-binding face of eIF1 was identified, interfaces to other preinitiation complex components and their relevance to eIF1 function have not been determined. Exploiting the solution structure of yeast eIF1, here we locate the binding site for eIF5 in its N-terminal tail and at a basic/hydrophobic surface area termed KH, distinct from the ribosome-binding face. Genetic and biochemical studies indicate that the eIF1 N-terminal tail plays a stimulatory role in cooperative multifactor assembly. A mutation altering the basic part of eIF1-KH is lethal and shows a dominant phenotype indicating relaxed start codon selection. Cheung et al. recently demonstrated that the alteration of hydrophobic residues of eIF1 disrupts a critical link to the preinitiation complex that suppresses eIF1 release before start codon selection (Cheung, Y.-N., Maag, D., Mitchell, S. F., Fekete, C. A., Algire, M. A., Takacs, J. E., Shirokikh, N., Pestova, T., Lorsch, J. R., and Hinnebusch, A. (2007) Genes Dev. 21, 1217-1230 ). Interestingly, eIF1-KH includes the altered hydrophobic residues. Thus, eIF5 is an excellent candidate for the direct partner of eIF1-KH that mediates the critical link. The direct interaction at eIF1-KH also places eIF5 near the decoding site of the 40 S subunit.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Reibarkh
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Chingakham Ranjit
authors.initials: CR
authors.lastname: Singh
authors.forename: Federico
authors.initials: F
authors.lastname: del Rio
authors.forename: Amr
authors.initials: A
authors.lastname: Fahmy
authors.forename: Bumjun
authors.initials: B
authors.lastname: Lee
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Luna
authors.forename: Miki
authors.initials: M
authors.lastname: Ii
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Katsura
authors.initials: K
authors.lastname: Asano
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D015977:Eukaryotic Initiation Factor-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D040061:Eukaryotic Initiation Factor-5 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010957:Plasmids; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012996:Solutions
chemical_list: D015977:Eukaryotic Initiation Factor-1; D040061:Eukaryotic Initiation Factor-5; D005656:Fungal Proteins; D012996:Solutions