Structure of interleukin 4 mutant E9A suggests polar steering in receptor-complex formation.

Interleukin 4 (IL-4) is a pleiotropic cytokine which induces T-cell differentiation and class switching of B cells. It therefore plays a central role in the development of allergies and asthma. An IL-4 variant in which Glu9 was mutated to alanine shows an 800-fold drop in binding affinity towards its high-affinity receptor chain. As shown by surface plasmon resonance measurements, this mostly arises from a decreased association rate. Here, the crystal structure of this mutant is reported. It reveals that the protein has a virtually identical structure to the wild type, showing that the unusual behaviour of the mutated protein is not a consequence of misfolding. The possibility that polar interactions in the encounter complex have a steering effect is discussed.