Identification of regions within the third FnIII-like domain of the IL-5Rα involved in IL-5 interaction

Abstract

Previously, two binding sites for interleukin 5 (IL-5) were identified on the IL-5 receptor alpha chain (IL-5Rα). They are located within the CD loop of the first fibronectin type III (FnIII)-like domain and the EF loop of the second FnIII-like domain. The first binding site was identified by exploiting the different abilities of human IL-5Rα (hIL-5Rα) and mouse IL-5Rα (mIL-5Rα) to bind hIL-5. Here we show that ovine IL-5 (oIL-5) has the ability to activate the hIL-5Rα but not the mIL-5Rα. By using chimeras of the mIL-5Rα and hIL-5Rα we demonstrate that residues within the first and third FnIII-like domains of mIL-5Rα are responsible for this lack of activity. Furthermore, mutation of residu..