Secondary structure and topology of human interleukin 4 in solution

Authors:
  • LSLorna J. Smith
    Lorna J. Smith
  • JBJonathan Boyd
    Jonathan Boyd
  • GLG. Mark P. Lawrence
    G. Mark P. Lawrence
  • RERobert G. Edwards
    Robert G. Edwards
  • RSRichard A. G. Smith
    Richard A. G. Smith
  • CDChristopher M. Dobson
    Christopher M. Dobson
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Abstract
Human interleukin 4 (IL-4) has been studied by 2D and 3D NMR techniques using uniformly 15N-labeled recombinant protein. Assignment of resonances for all but 3 of the 130 residues of the recombinant protein has been achieved, enabling the secondary structure of the protein to be defined. This consists of four major alpha-helical regions and one short section of double-stranded antiparallel beta-sheet. Analysis of distance and angle restraints derived from NMR experiments has enabled the overall molecular topology to be determined. This is related to that found for other four-helix proteins but has several distinctive features including cross-linking of helices by means of three disulfide bonds and a short section of beta-sheet. The structural analysis gives support to the hypothesis that many helical cytokines have a common fold and provides a basis for understanding the biological function of IL-4.