Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface.
Interleukin-4 (IL-4) is a principal regulatory cytokine during an immune response and a crucial determinant for allergy and asthma. IL-4 binds with high affinity and specificity to the ectodomain of the IL-4 receptor alpha chain (IL4-BP). Subsequently, this intermediate complex recruits the common gamma chain (gamma c), thereby initiating transmembrane signaling. The crystal structure of the intermediate complex between human IL-4 and IL4-BP was determined at 2.3 A resolution. It reveals a novel spatial orientation of the two proteins, a small but unexpected conformational change in the receptor-bound IL-4, and an interface with three separate clusters of trans-interacting residues. Novel insights on ligand binding in the cytokine receptor family and a paradigm for receptors of IL-2, IL-7, IL-9, and IL-15, which all utilize gamma c, are provided.
Hage
T
T
Institut für Physiologische Chemie II, Theodor-Boveri-Institut für Biowissen Schaften (Biozentrum), Universität Würzburg, Germany.
Sebald
W
W
Reinemer
P
P
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D046911:Macromolecular Substances; D018121:Receptors, Cytokine; D019948:Receptors, Interleukin-4; D015847:Interleukin-4