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Molecular mechanism of glycosylated IL-1RII counteraction with IL-1RI in regulation of the immune response

Jamshidi Khameneh, N ; Sharif University of Technology | 2023

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  1. Type of Document: Article
  2. DOI: 10.1080/08927022.2023.2243339
  3. Publisher: Taylor and Francis Ltd , 2023
  4. Abstract:
  5. Interleukin-1 Receptor Type II (IL-1RII) is the decoy receptor of IL-1 cytokines. It down-regulates the immune signalling pathways. There is a competitive behaviour between the IL-1RII and IL-1RI, which is the signalling receptor of the IL-1Rs family. By adopting similarities in structure and specific shared ligands, the two receptors are competing regulators of the immune response. Conformational changes of IL-1RII is a crucial factor in its ligand binding and activation. In addition, dynamics and functionality of the receptor are known to be regulated by glycosylation. Herein, all-atom Molecular Dynamics (MD) simulations were carried out to investigate the dynamics of the apo and cytokine-bound IL-1RII upon full glycosylation. Simulations showed that the IL-1RII presents two extended/active and compact/inactive conformations. Glycosylation maintains the conformation in the extended/active state. Furthermore, It was shown that IL-1 cytokine binding to IL-1RII contributes to stabilisation of the receptor. Comparison of IL-1RI and IL-1RII interaction with IL-1β at the equilibrium condition predicted that glycosylation could increase the binding possibility of IL-1RII towards its ligand. That supports preservation of the active/extended conformation by glycosylation as observed in MD simulations. © 2023 Informa UK Limited, trading as Taylor & Francis Group
  6. Keywords:
  7. Glycosylation ; IL-1RII ; Immune response ; Molecular dynamics simulation
  8. Source: Molecular Simulation ; Volume 49, Issue 16 , 2023 , Pages 1491-1501 ; 08927022 (ISSN)
  9. URL: https://www.tandfonline.com/doi/abs/10.1080/08927022.2023.2243339