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Glycan-mediated functional assembly of IL-1RI: structural insights into completion of the current description for immune response

Azimzadeh Irani, M ; Sharif University of Technology | 2022

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  1. Type of Document: Article
  2. DOI: 10.1080/07391102.2020.1841027
  3. Publisher: Taylor and Francis Ltd , 2022
  4. Abstract:
  5. Interleukin 1 Receptor type I (IL-1RI) is a multi-domain transmembrane receptor that triggers the inflammatory response. Understanding its detailed mechanism of action is crucial for treating immune disorders. IL-1RI is activated upon formation of its functional assembly that occurs by binding of the IL-1 cytokine and the accessory protein (Il-1RAcP) to it. X-ray crystallography, small-Angle X-ray Scattering and molecular dynamics simulation studies showed that IL-1RI adopts two types of ‘compact’ and ‘extended’ conformational states in its dynamical pattern. Furthermore, glycosylation has shown to play a critical role in its activation process. Here, classical and accelerated atomistic molecular dynamics were carried out to examine the role of full glycosylation of IL-1RI and IL-1RAcP in arrangement of the functional assembly. Simulations showed that the ‘compact’ and ‘extended’ IL-1RI form two types of ‘cytokine-inaccessible-non-signaling’ and ‘cytokine-accessible-signaling’ assemblies with the IL-1RacP, respectively that are both abiding in the presence of glycans. Suggesting that the cytokine binding to IL-1RI is not required for the formation of IL-1RI-IL-1RAcP complex and the ‘compact’ complex could act as a down-regulatory mechanism. The ‘extended’ complex is maintained by formation of several persistent hydrogen bonds between the IL-1RI-IL-1RAcP inter-connected glycans. Taken together, it was shown that full glycosylation regulates formation of the IL-1RI functional assembly and play critical role in cytokine biding and triggering the IL-1RI involved downstream pathways in the cell. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group
  6. Keywords:
  7. Glycosylation ; IL-1RAcP ; IL-1RI functional assembly ; Molecular dynamics simulation ; Cytokine ; Glycan ; Glycan derivative ; Hydrogen ; Interleukin 1 receptor type I ; Interleukin 1 receptor accessory protein ; Polysaccharide ; Protein binding ; Carbohydrate analysis ; Down regulation ; Hydrogen bond ; Immune response ; Molecular dynamics ; Protein assembly ; Protein function ; Protein glycosylation ; Protein structure ; Receptor binding ; Signal transduction ; Simulation ; Chemistry ; Metabolism ; Cytokines ; Immunity ; Interleukin-1 Receptor Accessory Protein ; Polysaccharides ; Receptors, Interleukin-1 Type I
  8. Source: Journal of Biomolecular Structure and Dynamics ; Volume 40, Issue 6 , 2022 , Pages 2575-2585 ; 07391102 (ISSN)
  9. URL: https://www.tandfonline.com/doi/abs/10.1080/07391102.2020.1841027