Complete 1H, 15N and 13C assignments, secondary structure, and topology of recombinant human interleukin-6.
Essentially complete backbone and side-chain 1H, 15N and 13C resonance assignments for the 185-amino-acid 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 alpha-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.
Small Molecule Drug Discovery Group, Genetics Institute, Cambridge, MA 02140, USA.
G Y
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Xu
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J
Hong
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McDonagh
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M
Stahl
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Kay
J
J
Seehra
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Cumming
D000595:Amino Acid Sequence; D002244:Carbon / Q000737:chemistry; D002247:Carbon Isotopes; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D015850:Interleukin-6 / Q000737:chemistry* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000737:chemistry; D009587:Nitrogen Isotopes; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D013499:Surface Properties
D002247:Carbon Isotopes; D015850:Interleukin-6; D009587:Nitrogen Isotopes; D011994:Recombinant Proteins; D002244:Carbon; D006859:Hydrogen; D009584:Nitrogen