Structural model of human IL-13 defines the spatial interactions with the IL-13Ralpha/IL-4Ralpha receptor.
Interleukin-13 (IL-13) plays a key role in immune responses and inflammation. A structural model of human IL-13 (HuIL-13) based on the nuclear magnetic resonance and X-ray structure of IL-4 is put forward. Unlike previous models, this model is based on new sequence alignments that take into account the formation of the two disulfide linkages that have been determined experimentally. The proposed structure of human IL-13 is similar to IL-4, consisting of a four helix bundle with hydrophobic residues lining the core of the molecule and surface polar residues showing a high degree of solvent accessibility. Regions of HuIL-13 that are critical for the interaction with its receptors are explored and discussed in relation to existing mutagenic studies. From these studies we predict that helices A and C of HuIL-13 interact with the IL-4 receptor alpha (IL-4Ralpha) region and helix D is responsible for the interaction with the IL-13 receptor alpha 1 (IL-13Ralpha1) receptor.
Zuegg
J
J
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research and Research School of Chemistry, Australian National University, Canberra, Australian Capital Territory, Australia.
Webb
D C
DC
Foster
P S
PS
Casarotto
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D018793:Interleukin-13 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D016415:Sequence Alignment; D012984:Software
C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4