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.
Hülsmeyer
M
M
Physiologische Chemie II, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. martin.huelsmeyer@charite.de
Scheufler
C
C
Dreyer
M K
MK
D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D003460:Crystallization; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D015847:Interleukin-4 / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry
D011994:Recombinant Proteins; D015847:Interleukin-4; D018698:Glutamic Acid; D000409:Alanine