An Interspecies Analysis Reveals Molecular Construction Principles of Interleukin 27
| Autor: | Matthias J. Feige, Stephanie I. Müller, Isabel Aschenbrenner, Martin Zacharias |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Interleukin-27
Protein Conformation Protein subunit Conserved sequence 03 medical and health sciences 0302 clinical medicine Species Specificity Structural Biology Animals Humans Macromolecular docking Secretion Disulfides Interleukin 27 Molecular Biology 030304 developmental biology 0303 health sciences Chemistry Interleukin EBI3 Cell biology Molecular Docking Simulation Protein Subunits Protein Multimerization 030217 neurology & neurosurgery Biogenesis |
| Zdroj: | Journal of molecular biology. 431(12) |
| ISSN: | 1089-8638 |
| Popis: | Interleukin 27 (IL-27) is a cytokine that regulates inflammatory responses. It is composed of an α subunit (IL-27α) and a β subunit (EBI3), which together form heterodimeric IL-27. Despite this general principle, IL-27 from different species shows distinct characteristics: Human IL-27α is not secreted autonomously while EBI3 is. In mice, the subunits show a reciprocal behavior. The molecular basis and the evolutionary conservation of these differences have remained unclear. They are biologically important, however, since secreted IL-27 subunits can act as cytokines on their own. Here, we show that formation of a single disulfide bond is an evolutionary conserved trait, which determines secretion-competency of IL-27α. Furthermore, combining cell-biological with computational approaches, we provide detailed structural insights into IL-27 heterodimerization and find that it relies on a conserved interface. Lastly, our study reveals a hitherto unknown construction principle of IL-27: one secretion-competent subunit generally pairs with one that depends on the other to induce its secretion. Taken together, these findings significantly extend our understanding of IL-27 biogenesis as a key cytokine and highlight how protein assembly can influence immunoregulation. |
| Databáze: | OpenAIRE |
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