Conservation of functional sites on interleukin-6 and implications for evolution of signaling complex assembly and therapeutic intervention

Abstract

Background: Interleukin-6 signaling requires assembly of a ternary IL-6/IL-6Rα/gp130 complex. Results: Determination of the mIL-6 structure allowed detailed structural and sequence comparisons with hIL-6, predicting the primacy of sites in driving IL-6/IL-6Rα-gp130 interactions, which was confirmed by binding experiments. Conclusion: Interactions between gp130 domain-1 and IL-6/IL-6Rα drive signaling complex assembly. Significance: This suggests a pathway for evolution of signaling complex assembly and strategies for therapeutic targeting.