Protein_Domain

Part:BBa_K4803000

Designed by: Kotaro MURAI   Group: iGEM23_UTokyo   (2023-10-10)


gp130 (IL 6 receptor-beta) extracellular domain

Usage and Biology

Glycoprotein130 (gp130) is, known as interleukin 6 signal transducer(IL6ST) or Interleukin 6 Receptor-β (IL6R-β), one of the cytokine receptor which functions in mammalian cell. This protein is ubiquitously expressed in the human body and forms a gp130-IL6-gp80 trimer in the presence of IL6. The trimer also binds to each other to form a hexamer. This hexamer formation reaction mediates cytokine signaling by activating the associated cytosolic tyrosine kinase and subsequent modification of transcription factors [1][2][3].

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Figure 1. IL6 signaling

The sequence of this part is an extracellular domain generated by codon optimization of the gp130 cDNA described in [1], minus the 5' end signal and downstream of the transmembrane region. In UTokyo2023 project, this part was used as part of the MESA (Modular Extracellular Sensor Architecture) system. This part forms homodimers or heterodimers with gp80 (BBa_K4803001) in the presence of IL6, which allows intracellular proteases to act and release protein of interest into the cytosol.

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Figure 2. Overview of MESA system

Characterization

In UTokyo2023 project, the 3D structure of this part was predicted by LocalColabFold [4].

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Figure 3. Stereoscopically predicted gp130 in LocalColabFold


Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal BamHI site found at 9
    Illegal BamHI site found at 827
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]

References

[1] Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., & Kishimoto, T. (1990). Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell, 63(6), 1149-1157. https://doi.org/10.1016/0092-8674(90)90411-7

[2] Taga, T., & Kishimoto, T. (1997). Gp130 and the interleukin-6 family of cytokines. Annual review of immunology, 15(1), 797-819. https://doi.org/10.1146/annurev.immunol.15.1.797

[3] Kaur, S., Bansal, Y., Kumar, R., & Bansal, G. (2020). A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors. Bioorganic & medicinal chemistry, 28(5), 115327. https://doi.org/10.1016/j.bmc.2020.115327

[4] Mirdita, M., Schütze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., & Steinegger, M. (2022). ColabFold: Making protein folding accessible to all. Nature Methods, 19(6), 679-682. https://doi.org/10.1038/s41592-022-01488-1


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