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OX40-aptamer
Description
In 2013, Pratico et al. isolated the human OX40 (hOX40) aptamer using systematic evolution of ligands by exponential enrichment. This aptamer binds the target purified protein with high affinity [dissociation constants (Kd)<10 nM][1].SELEX
In 2011, Pratico et al. identified isolated specific sequences for targeting HA in a 40nt sequence pool through 9 and 11 rounds of selection[1].
Detailed information are accessible on SELEX page.
Structure
9C7 was the aptamer sequence mainly studied in the article, which had a high affinity with OX40. The 2D structure of the figure is based on the article by ribodraw tool to draw[1].5'-AAAAAAGAACACUUCCGAUUAGGGCCCACCCUAACGGCCGCAG-3'
Ligand information
SELEX ligand
TNFRSF4 (also known as OX40, ACT35, CD134, IMD16, TXGP1L) activates NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. It also promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. It is primarily expressed on activated CD4+ and CD8+ T cells, where it is transiently expressed and upregulated on the most recently antigen-activated T cells within inflammatory lesions. This makes it an attractive target to modulate immune responses, i.e. TNFRSF4 (OX40) blocking agents to inhibit adverse inflammation or agonists to enhance immune responses. An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Some single nucleotide polymorphisms (SNPs) of its natural ligand OX40 ligand (OX40L, CD252), which is also found on activated T cells, have been associated with systemic lupus erythematosus.-----from Pfam
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| OX40 | P43489 | CD13406 | 17.00 kDa | LHCVGDTYPSNDRCCHECRPGNGLVSRCSRSQNTVCRPCGPGFYNDVVSSKPCKPCTWCNLRSGSERKQLCTATQDTVCRCRAGTQPLDSYKPGVDCAPCPPGHFSPGDNQACKPWTNCTLAGKHTLQPASNSSDAICEDRDMDPGGSHHHHHHHH | 8AG1 | 7YK4_A |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| 9C7 | 5'-AAAAAAGAACACUUCCGAUUAGGGCCCACCCUAACGGCCGCAG-3' | hOX40 | 1.7 nM |
| 11F11 | 5'-AACGGGACCACCCAUGCCAGGGGACCACCUCAGGCAGCGCCAGACGAC-3' | hOX40 | 10 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 |
|---|---|---|---|
| 2HEV-R | 15.5 | 2.4 | Tumor necrosis factor ligand superfamily member 4 |
| 6PE9-G | 10.0 | 2.7 | Fab heavy chain |
| 4YN0-A | 9.7 | 2.7 | Tumor necrosis factor receptor superfamily member |
| 3ALQ-S | 9.5 | 3.1 | Tumor necrosis factor |
| 1EXT-A | 9.3 | 4.3 | Tumor necrosis factor receptor |
| 7KX0-D | 9.2 | 2.2 | Cd70 antigen |
| 3ME4-A | 9.1 | 4.7 | Tumor necrosis factor receptor superfamily member |
| 7MSG-D | 8.7 | 2.4 | Tumor necrosis factor ligand superfamily member 1 |
| 2UWI-A | 8.6 | 4.1 | Crme protein |
| 4KGQ-D | 8.3 | 3.4 | Tumor necrosis factor receptor superfamily member |
References
[1] Identification and characterization of an agonistic aptamer against the T cell costimulatory receptor, OX40.Pratico, ED., Sullenger, BA., & Nair, SK.
Nucleic Acid Therapeutics, 23(1):35-43. (2013)