Structural model of human IL-13 defines the spatial interactions with the IL-13R alpha/IL-4R alpha receptor

Interleukin-13 (IL-13) plays a key role in immune responses and inflammatio n. A structural model of human IL-13 (HuIL-13) based on the nuclear magneti c resonance and X-ray structure of IL-4 is put forward. Unlike previous mod els, this model is based on new sequence alignments that take into account the formation of the two disulfide linkages that have been determined exper imentally. The proposed structure of human IL-13 is similar to IL-4, consis ting of a four helix bundle with hydrophobic residues lining the core of th e molecule and surface polar residues showing a high degree of solvent acce ssibility. Regions of HuIL-13 that are critical for the interaction with it s receptors are explored and discussed in relation to existing mutagenic st udies. From these studies we predict that helices A and C of HuIL-13 intera ct with the IL-4 receptor alpha (IL-4R alpha) region and helix D is respons ible for the interaction with the IL-13 receptor alpha 1 (IL-13R alpha1) re ceptor.