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Complete 1H, 15N and 13C assignments, secondary structure, and topology of recombinant human interleukin-6

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Summary

Essentially complete backbone and side-chain 1H, 15N and 13C resonance assignments for the 185-aminoacid cytokine interleukin-6 (IL-6) are presented. NMR experiments were performed on uniformly [15N]-and [15N, 13C]-labeled recombinant human IL-6 (rIL-6) using a variety of heteronuclear NMR experiments. A combination of 13C-chemical shift, amide hydrogen-bond exchange, and 15N-edited NOESY data allowed for analysis of the secondary structure of IL-6. The observed secondary structure of IL-6 is composed of loop regions connecting five α-helices, four of which are consistent in their length and disposition with the four-helix bundle motif present in other related cytokines and previously postulated for IL-6. In addition, the topology of the overall fold was found to be consistent with a left-handed up-up-down-down four-helix bundle based on a number of long-range interhelical NOEs. The results presented here provide deeper insight into structure-function relationships among members of the four-helix bundle family of proteins.

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Authors and Affiliations

  1. Small Molecule Drug Discovery Group, Genetics Institute, 87 CambridgePark Drive, 02140, Cambridge, MA, USA

    Guang-Yi Xu, Jin Hong, Tom McDonagh, Mark Stahl, Jasbir Seehra & Dale A. Cumming

  2. Department of Medical Genetics, Biochemistry and Chemistry, University of Toronto, M5S 1A8, Toronto, ON, Canada, Canada

    Lewis E. Kay

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  1. Guang-Yi Xu
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  2. Jin Hong
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Xu, GY., Hong, J., McDonagh, T. et al. Complete 1H, 15N and 13C assignments, secondary structure, and topology of recombinant human interleukin-6. J Biomol NMR 8, 123–135 (1996). https://doi.org/10.1007/BF00211159

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  • DOI: https://doi.org/10.1007/BF00211159

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