Insight into the structures of Interleukin-18 systems. (October 2020)

• Record Type: Journal Article
• Authors: Roy, Urmi
• Is Part Of: Computational biology and chemistry. Volume 88(2020)
• Publication Date: 2020-10
• Subjects: Structural biology -- Bioinformatics -- Interleukin-18 -- Interleukin-18 receptor -- Protein-protein interaction; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2020.107353
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: Interleukin-18 (IL-18) is a pro-inflammatory cytokine. Receptor/IL-18 binding initiates cell signaling pathways. Conformational changes of the ligand-protein upon receptor binding are described. Abstract: Structure-based molecular designs play a critical role in the context of next generation drug development. Besides their fundamental scientific aspects, the findings established in this approach have significant implications in the expansions of target-based therapies and vaccines. Interleukin-18 (IL-18), also known as interferon gamma (IFN-γ) inducing factor, is a pro-inflammatory cytokine. The IL-18 binds first to the IL-18α receptor and forms a lower affinity complex. Upon binding with IL-18β a hetero-trimeric complex with higher affinity is formed that initiates the signal transduction process. The present study, including structural and molecular dynamics simulations, takes a close look at the structural stabilities of IL-18 and IL-18 receptor-bound ligand structures as functions of time. The results help to identify the conformational changes of the ligand due to receptor binding, as well as the structural orders of the apo and holo IL-18 protein complexes.