A receptor-binding peptide from human interleukin-6: isolation and a proton nuclear magnetic resonance study.
In order to locate the receptor-binding region of human interleukin-6 (IL-6), twelve peptide fragments were prepared by digestion of IL-6 with lysylendopeptidase. A significant activity of the receptor-binding was observed only for a peptide Ile88-Lys121, although the activity was estimated at 10(4)-fold less than that of intact IL-6. Solution structure of the peptide Ile88-Lys121 was analyzed by using two-dimensional nuclear magnetic resonance (NMR) spectroscopy. The results indicate the presence of alpha-helices in the regions Leu93-Phe106 and Glu110-Ser119. On the basis of the NMR data, we also prepared two peptides. Four-fold less binding activity than that of the peptide Ile88-Lys121 was observed for the peptide Ile88-Arg105, but no activity for the peptide Glu110-Lys121. These results suggest that the helical peptide Ile88-Arg105 composes a part of the receptor-binding region.
Ekida
T
T
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Nishimura
C
C
Masuda
S
S
Itoh
S
S
Shimada
I
I
Arata
Y
Y
D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008961:Models, Structural; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011971:Receptors, Immunologic / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D012697:Serine Endopeptidases
D015850:Interleukin-6; D010446:Peptide Fragments; D010455:Peptides; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D012697:Serine Endopeptidases; C036813:lysyl endopeptidase