140
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.
