Critical role of the C-terminus in the biological activities of human tumour necrosis factor-alpha.
Alterations of the C-terminal amino acid sequence of human tumour necrosis factor-alpha (hTNF-alpha) caused significant changes in its biological activity. Thus shortening of the C-terminus by removal of two or three amino acids led to a very marked loss of cytotoxic activity. Other, more subtle changes introduced by site-directed mutagenesis resulted in a less drastic reduction in cytotoxicity. The mitogenic activity towards human fibroblasts of the hTNF-alpha was reduced in parallel with the loss of cytotoxicity. These results suggest that the C-terminal amino acids of hTNF-alpha are critical for its biological actions and that they may be part of the receptor-binding site.
Gase
K
K
Zentralinstitut für Mikrobiologie und Experimentelle Therapie, Akademie der Wissenschaften der DDR, Jena.
Korobko
V G
VG
Wisniewski
H G
HG
Le
J
J
Dobrynin
V N
VN
Filippov
S A
SA
Gutsche
W
W
Maksimova
Y N
YN
Schlott
B
B
Shingarova
L N
LN
D000595:Amino Acid Sequence; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008938:Mitosis / Q000276:immunology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000276:immunology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha