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eIF4E-aptamer
Description
In 2005, Mochizuki, K., & Nakamura, Y. developed two RNA aptamers, aptamer 1 and aptamer 2, with high affinity for mammalian eIF4E by in vitro RNA selection-amplification. Aptamer 1 inhibits the cap binding to eIF4E more efficiently than the cap analog m7GpppN or aptamer 2. Consistently, aptamer 1 inhibits specifically cap-dependent in vitro translation while it does not inhibit cap-independent HCV IRES-directed translation initiation[1].SELEX
In 2005, Mochizuki, K., & Nakamura, Y. cloned and sequenced 144 individual RNAs poolthrough 14 rounds of selection,revealing nine unique aptamers that did not share any common motifs .When these RNA species were labeled with [α-32P]CTP and examined for their ability to bind to eIF4E in a nitrocellulose filter retention assay, only two RNAs, no. 15 and no. 34, bound efficiently to eIF4E[1].
Detailed information are accessible on SELEX page.
Structure
The 2D structure of the figure is based on the article by ribodraw tool to draw[1].5'-GGGAGACAAGAAUAAACGCUCAAUGUUCAACCAGAGUGAAACCACUAACGGGUCAGAGCCCCUUCGACAGGAGGCUCACAACAGGC-3'
Ligand information
SELEX ligand
EIF4E-T is the transporter protein for shuttling the mRNA cap-binding protein EIF4E protein, targeting it for nuclear import. EIF4E-T contains several key binding domains including two functional leucine-rich NESs (nuclear export signals) between residues 438-447 and 613-638 in the human protein. The other two binding domains are an EIF4E-binding site, between residues 27-42 in Q9EST3, and a bipartite NLS (nuclear localisation signals) between 194-211, and these lie in family EIF4E-T_N. EIF4E is the eukaryotic translation initiation factor 4E that is the rate-limiting factor for cap-dependent translation initiation.-----from Pfam
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| eIF4E | P63074 | PF10477 | 25 kDa | MATVEPETTPTTNPPPAEEEKTESNQEVANPEHYIKHPLQNRWALWFFKNDKSKTWQANLRLISKFDTVEDFWALYNHIQLSSNLMPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQQRRSDLDRFWLETLLCLIGESFDDYSDDVCGAVVNVRAKGDKIAIWTTECENRDAVTHIGRVYKERLGLPPKIVIGYQSHADTATKSGSTTKNRFVV | 2WMC | 117045 |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| aptamer1 | 5'-GGGAGACAAGAAUAAACGCUCAAUGUUCAACCAGAGUGAAACCACUAACGGGUCAGAGCCCCUUCGACAGGAGGCUCACAACAGGC-3' | eIF4E | 11.2 nM |
Similar compound
We used the Dail server website to compare the structural similarities of ligand proteins, and chose the top 10 in terms of similarity for presentation. The Dali server is a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB). Z-score is a standard score that is converted from an original score. The list of neighbours is sorted by Z-score. Similarities with a Z-score lower than 2 are spurious. RMSD(Root Mean Square Deviation) value is used to measure the degree to which atoms deviate from the alignment position.
| PDB | Z-socre | RMSD | Description |
|---|---|---|---|
| 2GPQ-A | 15.5 | 3.1 | Eukaryotic translation initiation factor 4e |
| 7KCJ-A | 14.6 | 2.8 | Eukaryotic translation initiation factor 4e type |
| 1AP8-A | 12.8 | 3.4 | Translation initiation factor eif4e |
| 1ZTP-B | 10.3 | 2.8 | Basophilic leukemia expressed protein bles03 |
| 4RSX-A | 8.1 | 3.8 | Type iii effector hopa1 |
| 8SAM-A | 7.3 | 3.3 | Class iii lanthipeptide, class iii lanthionine sy |
| 3C19-A | 6.3 | 2.3 | Uncharacterized protein mk0293 |
| 3BO6-A | 6.1 | 3.3 | Hydrophilic protein, vira protein |
| 4DJB-A | 6.0 | 2.6 | E4-orf3 |
| 4AE5-B | 5.3 | 3.7 | Signal transduction protein trap |
References
[1] High affinity RNA for mammalian initiation factor 4E interferes with mRNA-cap binding and inhibits translation.Mochizuki,& Nakamura, Y.
RNA (New York, N.Y.), 11(1), 77–89. (2005)