Solution structure of synthetic peptides corresponding to the C-terminal helix of interleukin-6.
Two synthetic peptides corresponding to the C-terminal 19 residues of human and murine interleukin-6, respectively, have been synthesized and their structures in solution investigated using high-resolution 1H-NMR spectroscopy. Both peptides show a marked dependence of chemical-shift dispersion on pH, with a greater degree of structure apparent above pH 4.5, where their glutamate carboxyl groups are ionised. In purely aqueous solution, neither peptide adopts a well-defined structure, although the murine peptide has characteristics of a nascent helix. Titration of the murine peptide with trifluoroethanol produced a significant increase in structure, which was then investigated using two-dimensional NMR. In 50% (by vol.) trifluoroethanol the murine peptide consists of a well-defined central helix of 12 residues with unstructured N-terminal and C-terminal regions. These observations lend experimental support to the current model of the interleukin-6 structure, which proposes a four-helical bundle with the last helix encompassing the C-terminal 20-30 residues. Furthermore, the fact that synthetic peptides corresponding to part of the putative receptor-binding surface of interleukin-6 are able to adopt a similar conformation in solution to that proposed for the intact protein suggests that such peptide analogues should be useful starting points in the design of peptide agonists and antagonists of interleukin-6.
Morton
C J
CJ
Joint Protein Structure Laboratory, Ludwig Institute for Cancer Research, Parkville, Australia.
Simpson
R J
RJ
Norton
R S
RS
D000818:Animals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015850:Interleukin-6 / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D014270:Trifluoroethanol
D015850:Interleukin-6; D010446:Peptide Fragments; D014270:Trifluoroethanol