Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

87-POS Board 40 Structure and Dynamics of IL-1β and IL-1Ra Complexes with IL-1RI Examined by Molecular Dynamics Simulation Aysegul Turupcu , Prof. Burak Erman, Assoc. Prof. Mehmet Sayar. Koç University, Istanbul, Turkey. Interleukin-1 (IL-1) family cytokines lead to inflammation and mediate immune responses. IL-1 family proteins have naturally occurring antagonist which distinguish them from other cytokine families. IL-1β triggers signaling via binding to IL-1 receptor which result in recruitment of IL-1 accessory protein (AcP) to the extracellular domain of the receptor. This heterotrimeric complex formation is necessary for intracellular signal transduction. IL-1 receptor antagonist (IL-1Ra) competes for the same site of the receptor and blocks signaling. Although IL-1β and IL-1Ra have homologous structures, their complex structures revealed several distinct regions. We performed 200 ns molecular dynamics simulation of IL1β - IL1RI, IL1Ra - IL1RI and IL1β-IL1RI- IL1RAcP complexes to elucidate differences upon binding of agonist and antagonist. We show that when the antagonist is bound to the receptor, immunoglobin-like domain 3 of the IL-1RI has larger B-factors than when the receptor binds to the IL1β which can have an effect on recruitment of IL1RAcP. In addition, we reported correlation between key residues which are validated by mutagenesis studies to understand the dynamics of these complexes. This can provide information for selecting target in designing an inhibitor for inflammatory diseases caused by IL1β.

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