Role of leucine residues in the C-terminal region of human interleukin-6 in the biological activity.
Site-directed mutagenesis of two sets of three periodic leucine residues which appear at every seventh position in the C-terminal region of human interleukin-6 (IL-6) was performed. Both receptor-binding and immunoglobulin (Ig)-induction activities of a triple mutant Leu168,175,182-->Val were only 1% compared with those of wild-type IL-6. However, the mutant Leu152,159,166-->Val had 13% receptor-binding and 2% Ig-induction activities of those of wild-type IL-6. In order to obtain more direct information on the receptor-binding region, we prepared two synthetic peptides. A significant binding activity was observed for the peptide Leu168-Met185, but not for the peptide Leu152-Arg169. These results indicate that leucine residues in the C-terminal region, especially Leu168, Leu175, and Leu182, play an important role in the receptor-binding and Ig-induction activities.
Nishimura
C
C
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Ekida
T
T
Nomura
K
K
Sakamoto
K
K
Suzuki
H
H
Yasukawa
K
K
Kishimoto
T
T
Arata
Y
Y
D000595:Amino Acid Sequence; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D001483:Base Sequence; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D004854:Herpesvirus 4, Human; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D007930:Leucine; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000138:chemical synthesis; D011971:Receptors, Immunologic / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D007930:Leucine