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

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Abstract

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 auniformly 13C,15N-labelled sample. Secondary structure elements were defined on the basisof chemical shifts, NH-CαH coupling constants, medium-range NOEs and the location ofslowly exchanging amide protons. The protein contains four α-helices, the relativeorientations of which were determined on the basis of long-range, interhelical NOEs. The fourhelices are arranged in an up-up-down-down orientation, as found in other four-helical bundlecytokines. The overall topology of MH35-LIF is similar to that of the X-ray crystallographicstructure for murine LIF [Robinson et al. (1994) Cell, 77, 1101–1116]. Differencesbetween the X-ray structure and the solution structure are evident in the N-terminal tail, wherethe solution structure has a trans-Pro17 compared with the cis-Pro17 found in the crystalstructure and the small antiparallel β-sheet encompassing residues in the N-terminus andCD loop in the crystal structure is less stable.

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  1. Biomolecular Research Institute, 343 Royal Parade, Parkville, VIC, 3052, Australia

    Mark G. Hinds, Till Maurer & and Raymond S. Norton

  2. The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia

    Jian-Guo Zhang & Nicos A. Nicola

  3. The Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia

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

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Hinds, M.G., Maurer, T., Zhang, JG. et al. Resonance assignments, secondary structure and topology of leukaemia inhibitory factor in solution. J Biomol NMR 9, 113–126 (1997). https://doi.org/10.1023/A:1018636018243

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