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TfR-ECD aptamer
Timeline
Both the RNA aptamer and the DNA aptamer used in these studies fulfilled that requirement: internalization of streptavidin–aptamer conjugates was not inhibited by transferrin-Fe+3 at a concentration similar to that found in mouse serum[3]
A second preparation of TfR-ECD had much tighter binding of transferrin (Kd in the nM range), similar to the binding of human TfR-ECD to transferrin[4]
Uptake of the FB4-streptavidin conjugate was not inhibited by methyl-β-cyclodextrin, a cholesterol-sequestering agent that inhibits the raft–caveolar pathway[5]
Description
In 2008, Chi-hong B Chen et al. used the SELEX method to isolate the aptamer with high compatibility for the Mouse transferrin receptor (TfR-ECD). Their target molecule for aptamer selection was the extracellular domain of the mouse transferrin receptor (TfR). This receptor, ubiquitous in mammalian cells, is essential for the delivery of iron to cells via binding and endocytosis of transferrin-Fe+3, release of iron in endosomes, and dissociation of apotransferrin at the cell surface[1,2].SELEX
In 2008, Chi-hong B Chen et al. select aptamers from very large random libraries by SELEX an iterative process of enriching the mixture in molecules with high binding affinity and selectivity against the desired target[6].
Detailed information are accessible on SELEX page.
Structure
The 2D structure of the figure is based on the article by ribodraw tool to draw[6].FB4: 5'-GGGCGAAUUCCGCGUGUGCUGAGGGCGGAAGAACUAAUUUGGGACGGAUUGCGGCCGUUGUCUGUGGCGUCCGUUCGGG-3'
FB4 (truncated version): 5'-GGACGGAUUGCGGCCGUUGUCUGUGGCGUCCGUUCG-3'
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Ligand information
SELEX ligand
TfR1 is a transmembrane glycoprotein composed of two disulfide-linked monomers joined by two disulfide bonds. Each monomer binds one holo-transferrin molecule creating an iron-Tf-TfR complex which enters the cell by endocytosis.-----From Wiki
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| Transferrin receptor 1 | Q62351 | IPR039373 | 85.74 kDa | MMDQARSAFSNLFGGEPLSYTRFSLARQVDGDNSHVEMKLAADEEENADNNMKASVRKPKRFNGRLCFAAIALVIFFLIGFMSGYLGYCKRVEQKEECVKLAETEETDKSETMETEDVPTSSRLYWADLKTLLSEKLNSIEFADTIKQLSQNTYTPREAGSQKDESLAYYIENQFHEFKFSKVWRDEHYVKIQVKSSIGQNMVTIVQSNGNLDPVESPEGYVAFSKPTEVSGKLVHANFGTKKDFEELSYSVNGSLVIVRAGEITFAEKVANAQSFNAIGVLIYMDKNKFPVVEADLALFGHAHLGTGDPYTPGFPSFNHTQFPPSQSSGLPNIPVQTISRAAAEKLFGKMEGSCPARWNIDSSCKLELSQNQNVKLIVKNVLKERRILNIFGVIKGYEEPDRYVVVGAQRDALGAGVAAKSSVGTGLLLKLAQVFSDMISKDGFRPSRSIIFASWTAGDFGAVGATEWLEGYLSSLHLKAFTYINLDKVVLGTSNFKVSASPLLYTLMGKIMQDVKHPVDGKSLYRDSNWISKVEKLSFDNAAYPFLAYSGIPAVSFCFCEDADYPYLGTRLDTYEALTQKVPQLNQMVRTAAEVAGQLIIKLTHDVELNLDYEMYNSKLLSFMKDLNQFKTDIRDMGLSLQWLYSARGDYFRATSRLTTDFHNAEKTNRFVMREINDRIMKVEYHFLSPYVSPRESPFRHIFWGSGSHTLSALVENLKLRQKNITAFNETLFRNQLALATWTIQGVANALSGDIWNIDNEF | 1CX8 | 22042 |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| FB4 | 5'-GGGCGAAUUCCGCGUGUGCUGAGGGCGGAAGAACUAAUUUGGGACGGAUUGCGGCCGUUGUCUGUGGCGUCCGUUCGGG-3' | Mouse transferrin receptor (TfR-ECD) | NA |
| FB4 (truncated version) | 5'-GGACGGAUUGCGGCCGUUGUCUGUGGCGUCCGUUCG-3' | Mouse transferrin receptor (TfR-ECD) | NA |
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 |
|---|---|---|---|
| 1CX8-A | 73.0 | 0.0 | Transferrin receptor protein |
| 2NSU-A | 63.6 | 0.1 | Transferrin receptor protein 1 |
| 1CX8-C | 63.6 | 0.3 | Transferrin receptor protein |
| 1CX8-B | 63.5 | 0.2 | Transferrin receptor protein |
| 1CX8-E | 63.4 | 0.2 | Transferrin receptor protein |
| 1SUV-B | 63.4 | 0.3 | Transferrin receptor protein 1 |
| 2NSU-B | 63.3 | 0.3 | Transferrin receptor protein 1 |
| 6OKD-B | 56.2 | 1.2 | Transferrin receptor protein 1 |
| 6WRW-B | 56.1 | 1.4 | Transferrin receptor protein 1 |
| 1DE4-I | 55.6 | 1.4 | Hemochromatosis protein |
References
[1] Receptor-mediated endocytosis of transferrin in K562 cells.Klausner, R. D., Van Renswoude, J., Ashwell, G., Kempf, C., Schechter, A. N., Dean, A., & Bridges, K. R.
The Journal of biological chemistry, 258(8), 4715–4724. (1983)
[2] pH and the recycling of transferrin during receptor-mediated endocytosis.
Dautry-Varsat, A., Ciechanover, A., & Lodish, H. F.
Proceedings of the National Academy of Sciences of the United States of America, 80(8), 2258–2262. (1983)
[3] Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia.
Bernstein S. E.
The Journal of laboratory and clinical medicine, 110(6), 690–705. (1987)
[4] Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.
Lebrón, J. A., Bennett, M. J., Vaughn, D. E., Chirino, A. J., Snow, P. M., Mintier, G. A., Feder, J. N., & Bjorkman, P. J.
Cell, 93(1), 111–123. (1998)
[5] Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms.
Parton, R. G., & Richards, A. A.
Traffic (Copenhagen, Denmark), 4(11), 724–738. (2003)
[6] Aptamer-based endocytosis of a lysosomal enzyme.
Chen, C. H., Dellamaggiore, K. R., Ouellette, C. P., Sedano, C. D., Lizadjohry, M., Chernis, G. A., Gonzales, M., Baltasar, F. E., Fan, A. L., Myerowitz, R., & Neufeld, E. F.
Proceedings of the National Academy of Sciences of the United States of America, 105(41), 15908–15913. (2008)