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Interleukin-6 receptor domain 3 (IL-6R D3)-aptamer
Description
In 2015, Florian Mittelberger and colleagues used SELEX (Systematic Evolution of Ligands by Exponential enrichment) technique to isolate high affinity RNA aptamers that bind to the IL-6R D3 protein[1].SELEX
In 2015, Florian Mittelberger and Cindy Meyer et al. isolated 35 specific sequences for targetingin Soluble pleiotropic cytokine interleukin-6 receptor (sIL-6R) and interleukin-6 receptor domain 3 (IL-6R D3) in 11 rounds of selection[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'-GGAAGAAAGAGGUCUGAGACAUUCUUAAAAACGGCCCAUCGUUUGGCGCUGUGGGAGUGGAGGGUGGAUGGUGUUAAGCGAUUGGCUUCUGGAGUUGACGUUGCUU-3'
Ligand information
SELEX ligand
Interleukin 6 (IL6) is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in immune response. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer.
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| Interleukin-6 receptor domain 3 (IL-6R D3) | P40189 | PF00041 | 103.537 kDa | MLTLQTWLVQALFIFLTTESTGELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHVNANYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLTCNILTFGQLEQNVYGITIISGLPPEKPKNLSCIVNEGKKMRCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPTSCTVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKPNPPHNLSVINSEELSSILKLTWTNPSIKSVIILKYNIQYRTKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIRCMKEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQGYRTVQLVWKTLPPFEANGKILDYEVTLTRWKSHLQNYTVNATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACDFQATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSDKAPCITDWQQEDGTVHRTYLRGNLAESKCYLITVTPVYADGPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWDQLPVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSLTSDTLYMVRMAAYTDEGGKDGPEFTFTTPKFAQGEIEAIVVPVCLAFLLTTLLGVLFCFNKRDLIKKHIWPNVPDPSKSHIAQWSPHTPPRHNFNSKDQMYSDGNFTDVSVVEIEANDKKPFPEDLKSLDLFKKEKINTEGHSSGIGGSSCMSSSRPSISSSDENESSQNTSSTVQYSTVVHSGYRHQVPSVQVFSRSESTQPLLDSEERPEDLQLVDHVDGGDGILPRQQYFKQNCSQHESSPDISHFERSKQVSSVNEEDFVRLKQQISDHISQSCGSGQMKMFQEVSAADAFGPGTEGQVERFETVGMEAATDEGMPKSYLPQTVRQGGYMPQ | 1BQU | 3572 |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| F4 | 5'-GGAAGAAAGAGGUCUGAGACAUUCUUAAAAACGGCCCAUCGUUUGGCGCUGUGGGAGUGGAGGGUGGAUGGUGUUAAGCGAUUGGCUUCUGGAGUUGACGUUGCUU-3' | Interleukin-6 receptor domain 3 (IL-6R D3) | 34.8 ± 5.8 nM |
| F2 | 5'-GGAAGAAAGAGGUCUGAGACAUUCUCAACGAACUAUGAGGAAAGGGACCGUGCGAGGGUUGGGUUAGGGUUUGGAGCCACGGUCCUUCUGGAGUUGACGUUGCUU-3' | Interleukin-6 receptor domain 3 (IL-6R D3) | 97.7 ± 18.3 nM |
| F3 | 5'-GGAAGAAAGAGGUCUGAGACAUUCUGAAGAGAGAAAGCCAGUAGAGGGAAGAGGGAUGAGGGACGUGGGAAUCUUGGUAAUCAGUCUUCUGGAGUUGACGUUGCUU-3' | Interleukin-6 receptor domain 3 (IL-6R D3) | 179 ± 117 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 |
|---|---|---|---|
| 8D82-A | 24.1 | 2.0 | Soluble interleukin-6 receptor subunit alpha |
| 7Z0L-B | 15.5 | 2.5 | Interleukin-6 receptor subunit beta |
| 6DG5-B | 15.5 | 3.9 | Neoleukin-2/15 |
| 6MOJ-B | 14.9 | 3.6 | Dimeric darpin acr5 (a_angle_r5) |
| 1N26-A | 14.8 | 5.6 | Il-6 receptor alpha chain |
| 7S2R-A | 14.5 | 2.7 | Cytokine receptor common subunit gamma |
| 7U7N-A | 14.5 | 2.3 | Interleukin-27 receptor subunit alpha |
| 3BPL-B | 14.1 | 3.6 | Interleukin-4 |
| 5MZV-C | 14.0 | 4.0 | Interleukin-12 subunit beta |
| 4DOH-E | 13.9 | 4.1 | Interleukin-20 |
References
[1] RAID3-An interleukin-6 receptor-binding aptamer with post-selective modification-resistant affinity.Mittelberger, F., Meyer, C., Waetzig, G. H., Zacharias, M., Valentini, E., Svergun, D. I., ... & Hahn, U.
RNA biology, 12(9), 1043-1053. (2015)