title: Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy.
abstract: The three-dimensional solution structure of recombinant human interleukin-4, a protein of 133 residues and 15.4 kilodaltons that plays a key role in the immune and inflammatory systems, has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is dominated by a left-handed four-helix bundle with an unusual topology comprising two overhand connections. The linker elements between the helices are formed by either long loops, small helical turns, or short strands. The overall topology is remarkably similar to that of growth hormone and granulocyte-macrophage colony stimulating factor, despite the absence of any sequence homology, and substantial differences in the relative lengths of the helices, the length and nature of the various connecting elements, and the pattern of disulfide bridges. These three proteins, however, bind to cell surface receptors belonging to the same hematopoietic superfamily, which suggests that interleukin-4 may interact with its receptor in an analogous manner to that observed in the crystal structure of the growth hormone-extracellular receptor complex.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: R
authors.initials: R
authors.lastname: Powers
authors.forename: D S
authors.initials: DS
authors.lastname: Garrett
authors.forename: C J
authors.initials: CJ
authors.lastname: March
authors.forename: E A
authors.initials: EA
authors.lastname: Frieden
authors.forename: A M
authors.initials: AM
authors.lastname: Gronenborn
authors.forename: G M
authors.initials: GM
authors.lastname: Clore
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D015847:Interleukin-4 / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry; D012996:Solutions
chemical_list: D011994:Recombinant Proteins; D012996:Solutions; D015847:Interleukin-4