title: Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy.
abstract: Cytokines are hormones that carry information from cell to cell. This information is read from their surface upon binding to transmembrane 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.
authors.affiliation: Theodor-Boveri-Institut für Biowissenschaften (Biozentrum) Universität Würzburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Dieckmann
authors.forename: W
authors.initials: W
authors.lastname: Sebald
authors.forename: H
authors.initials: H
authors.lastname: Oschkinat
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D013006:Growth Hormone / Q000737:chemistry; D006801:Humans; D015847:Interleukin-4 / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4; D013006:Growth Hormone