ASPECTS OF RECEPTOR-BINDING AND SIGNALING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR-SPECTROSCOPY

Cytokines are hormones that carry information from cell to cell. This information is read from their surface upon binding to trannsmembrane receptors and by the subsequent initiation of receptor oligomerization. An influence on this process through mutagenesis on the hormone surface is highly desirable for medical reasons. However, an understanding of hormone-receptor interactions requires insight into the structural changes introduced by the mutations. In this line structural studies on human IL-4 and the medically important IL-4 antagonists Y124D and Y124G are presented. The site around Y124 is an important epitope responsible for the ability of IL-4 to cause a signal in the target cells. It is shown that the local main-chain structure around residue 124 in the variants remains unchanged. A strategy is presented here which allows the study of these types of proteins and their variants by NMR which does not require carbon labelled samples. © 1994 Academic Press Limited.