Solution structure of human IL-13 and implication for receptor binding.
Interleukin-13 has been implicated as a key factor in asthma, allergy, atopy and inflammatory response, establishing the protein as a valuable therapeutic target. The high-resolution solution structure of human IL-13 has been determined by multidimensional NMR. The resulting structure is consistent with previous short-chain left-handed four-helix bundles, where a significant similarity in the folding topology between IL-13 and IL-4 was observed. IL-13 shares a significant overlap in biological function with IL-4, a result of the common alpha chain component (IL-4Ralpha) in their respective receptors. Based on the available structural and mutational data, an IL-13/IL-4Ralpha model and a sequential mechanism for forming the signaling heterodimer is proposed for IL-13.
Moy
F J
FJ
Department of Biological Chemistry,Wyeth Research, Cambridge, MA 02140, USA.
Diblasio
E
E
Wilhelm
J
J
Powers
R
R
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D018793:Interleukin-13 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D018123:Receptors, Interleukin / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D012996:Solutions
C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D012996:Solutions; D015847:Interleukin-4