Coding

Part:BBa_K5522000

Designed by: Hayashi Rika   Group: iGEM24_SHSID-China   (2024-08-26)

IL18-BPc


Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]

BBa_K5522000 (IL18-BPc)

Profile

Name: SUMO-IL18-BPc-Fc

Base Pairs: 1641bp

Origin: Homo sapiens

Properties

The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells, including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1 and is capable of stimulating interferon-gamma production and regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs and in potentially fatal conditions characterized by a cytokine storm. In humans, the IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene [1-2].

Usage and Biology

There are four different subtypes of human IL-18BP: IL-18BPa, IL-18BPb, IL-18BPc, and IL-18BPd. IL-18BPc can inhibit the biological function of IL-18, and human IL-18BPa shows the greatest affinity to IL-18, making it an ideal candidate drug for blocking IL-18 in the treatment of inflammatory bowel disease (IBD) [3-5].

In our project, the DNA sequence of the human IL-18BPc gene was obtained from the research article by Novick et al. The sequences coding for SUMO and IgG1 Fc were obtained from the NCBI Homo sapiens genome. The sequences were compiled in this fashion: SUMO-IL-18BPc-Fc. A 6×His tag was added to the C-terminal of the protein. The SUMO modification enhances the stability of the protein, while the Fc modification, as shown in other research, slows the degradation of proteins in vivo. The His tag is used for protein purification. Codon optimization improves gene expression and enhances translational efficiency within E. coli.

References

  1. Piersiala K, Hjalmarsson E, da Silva PFN, Lagebro V, Kolev A, Starkhammar M, Elliot A, Marklund L, Munck-Wikland E, Margolin G, Georén SK, Cardell LO. Regulatory B cells producing IL-10 are increased in human tumor draining lymph nodes. Int J Cancer. 2023 Aug 15;153(4):854-866. doi:10.1002/ijc.34555. Epub 2023 May 5. PMID: 37144812.
  2. Liang X, Fan Y. Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk. Front Immunol. 2023 May 25;14:1183378. doi:10.3389/fimmu.2023.1183378. PMID: 37304287; PMCID: PMC10247971.
  3. Menachem A, Alteber Z, Cojocaru G, et al. Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects. Cancer Immunology Research, 2024, OOF1-OF17.
  4. Yamanishi K, Hata M, Gamachi N, et al. Molecular Mechanisms of IL18 in Disease. Int J Mol Sci. 2023, 24(24).
  5. Ihim, S. A., Abubakar, S. D., Zian, Z., Sasaki, T., Saffarioun, M., Maleknia, S., & Azizi, G. (2022). Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment. Frontiers in Immunology, 13, 919973. doi:10.3389/fimmu.2022.919973

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