Reference: Singh CR, et al. (2004) Physical association of eukaryotic initiation factor (eIF) 5 carboxyl-terminal domain with the lysine-rich eIF2beta segment strongly enhances its binding to eIF3. J Biol Chem 279(48):49644-55

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Abstract


The carboxyl-terminal domain (CTD) of eukaryotic initiation factor (eIF) 5 interacts with eIF1, eIF2beta, and eIF3c, thereby mediating formation of the multifactor complex (MFC), an important intermediate for the 43 S preinitiation complex assembly. Here we demonstrate in vitro formation of a nearly stoichiometric quaternary complex containing eIF1 and the minimal segments of eIF2beta, eIF3c, and eIF5. In vivo, overexpression of eIF2 and tRNA(Met)(i) suppresses the temperature-sensitive phenotype of tif5-7A altering eIF5-CTD by increasing interaction of the mutant eIF5 with eIF2 by mass action and restoring its defective interaction with eIF3. By contrast, overexpression of eIF1 exacerbated the tif5-7A phenotype because eIF1 forms unusual inhibitory complexes with a hyperstoichiometric amount of eIF1. Formation of such complexes leads to increased GCN4 translation, independent of eIF2 phosphorylation (general control derepressed or Gcd(-) phenotype). We also provide biochemical evidence indicating that the association of eIF5-CTD with eIF2beta strongly enhances its binding to eIF3c. Our results suggest strongly that MFC formation is an ordered event involving specific enhancement of eIF5-CTD binding to eIF3 on its binding to eIF2beta. We propose that the primary function of eIF5-CTD is to serve as an assembly guide by rapidly promoting stoichiometric MFC assembly with the aid of eIF2 while excluding formation of nonfunctional complexes.

Reference Type
Journal Article | Research Support, U.S. Gov't, Non-P.H.S. | Research Support, U.S. Gov't, P.H.S.
Authors
Singh CR, Yamamoto Y, Asano K
Primary Lit For
Eukaryotic translation initiation factor 2 complex | Eukaryotic translation initiation factor 3 core complex
Additional Lit For
SUI1 | GCN4 | GCN2 | TIF5 | TIF34

Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 8 entries for 5 genes

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InteractorInteractorAssayAnnotationActionModification
NIP1TIF5Reconstituted Complexmanually curatedHit-BaitNo Modification
NIP1SUI1Reconstituted Complexmanually curatedBait-HitNo Modification
SUI1TIF5Reconstituted Complexmanually curatedBait-HitNo Modification
SUI1TIF5Reconstituted Complexmanually curatedHit-BaitNo Modification
SUI1SUI3Reconstituted Complexmanually curatedHit-BaitNo Modification
SUI3TIF5Reconstituted Complexmanually curatedHit-BaitNo Modification
TIF34TIF5Affinity Capture-Westernmanually curatedBait-HitNo Modification
TIF34SUI1Affinity Capture-Westernmanually curatedBait-HitNo Modification
Showing 1 to 8 of 8 entries