Resonance assignments, secondary structure and topology of leukaemia inhibitory factor in solution

Mark G. Hinds, Till Maurer, Jian Guo Zhang, Nicos A. Nicola, Raymond S. Norton

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The chemical shift assignments and secondary structure of a murine-human chimera, MH35, of leukaemia inhibitory factor (LIF), a 180-residue protein of molecular mass 20 kDa, have been determined from multidimensional heteronuclear NMR spectra acquired on a uniformly 13C,15N-labelled sample. Secondary structure elements were defined on the basis of chemical shifts, NH-CαH coupling constants, medium-range NOEs and the location of slowly exchanging amide protons. The protein contains four α-helices, the relative orientations of which were determined on the basis of long-range, interhelical NOEs. The four helices are arranged in an up-up-down-down orientation, as found in other four-helical bundle cytokines. The overall topology of MH35-LIF is similar to that of the X-ray crystallographic structure for murine LIF [Robinson et al. (1994) Cell, 77, 1101-1116]. Differences between the X-ray structure and the solution structure are evident in the N-terminal tail, where the solution structure has a trans-Pro17 compared with the cis-Pro17 found in the crystal structure and the small antiparallel β-sheet encompassing residues in the N-terminus and CD loop in the crystal structure is less stable.

Original languageEnglish
Pages (from-to)113-126
Number of pages14
JournalJournal of Biomolecular NMR
Issue number2
Publication statusPublished - 1997
Externally publishedYes


  • Chemical shift assignments
  • Cytokine
  • Helices
  • Heteronuclear NMR
  • Isotope labelling
  • Leukaemia inhibitory factor

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