Insertion of a Structural Domain of Interleukin (IL)-1β Confers Agonist Activity to the IL-1 Receptor Antagonist IMPLICATIONS FOR IL-1 BIOACTIVITY (∗)

We showed previously that replacement of Lys-145 in the IL-1 receptor antagonist (IL-1ra) with Asp resulted in an analog (IL-1ra K145D) with partial agonist activity. To identify additional amino acids that affect IL-1 bioactivity, we created second site mutations in IL-1ra K145D. Substitutions of single amino acids surrounding position 145 were made; none of these substitutions increased the bioactivity of IL-1ra K145D. However, the insertion …