Reference: Singh CR, et al. (2004)
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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
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Journal Article |
Research Support, U.S. Gov't, Non-P.H.S. |
Research Support, U.S. Gov't, P.H.S.
- Authors
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Singh CR,
Yamamoto Y,
Asano K
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- Eukaryotic translation initiation factor 2 complex | Eukaryotic translation initiation factor 3 core complex
- SUI1 | GCN4 | GCN2 | TIF5 | TIF34
Gene Ontology Annotations
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Evidence ID |
Analyze ID |
Gene/Complex |
Systematic Name/Complex Accession |
Qualifier |
Gene Ontology Term ID |
Gene Ontology Term |
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Annotation Extension |
Evidence |
Method |
Source |
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Analyze ID |
Gene |
Gene Systematic Name |
Phenotype |
Experiment Type |
Experiment Type Category |
Mutant Information |
Strain Background |
Chemical |
Details |
Reference |
Disease Annotations
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Evidence ID |
Analyze ID |
Regulator |
Regulator Systematic Name |
Target |
Target Systematic Name |
Direction |
Regulation of |
Happens During |
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Regulation Of |
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Post-translational Modifications
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Interaction Annotations
Genetic Interactions
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genes involved in the interaction.
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Analyze ID |
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Interactor |
Interactor Systematic Name |
Interactor |
Interactor Systematic Name |
Allele |
Assay |
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Action |
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SGA score |
P-value |
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Note |
Physical Interactions
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| Interactor | Interactor | Assay | Annotation | Action | Modification |
| NIP1 | TIF5 | Reconstituted Complex | manually curated | Hit-Bait | No Modification |
| NIP1 | SUI1 | Reconstituted Complex | manually curated | Bait-Hit | No Modification |
| SUI1 | TIF5 | Reconstituted Complex | manually curated | Bait-Hit | No Modification |
| SUI1 | TIF5 | Reconstituted Complex | manually curated | Hit-Bait | No Modification |
| SUI1 | SUI3 | Reconstituted Complex | manually curated | Hit-Bait | No Modification |
| SUI3 | TIF5 | Reconstituted Complex | manually curated | Hit-Bait | No Modification |
| TIF34 | TIF5 | Affinity Capture-Western | manually curated | Bait-Hit | No Modification |
| TIF34 | SUI1 | Affinity Capture-Western | manually curated | Bait-Hit | No Modification |
Functional Complementation Annotations
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Complement ID |
Locus ID |
Gene |
Species |
Gene ID |
Strain background |
Direction |
Details |
Source |
Reference |