Escherichia coli LT enterotoxin subunit A demonstrates partial toxicity independent of the nicking around Arg192.
A study was conducted into whether or not nicking of the A subunit of Escherichia coli LT enterotoxin at position Arg192 or its neighbouring amino acids Arg192 to The195 is required for its toxicity. The toxic activity of mutants created by substitution or deletion at this position, which lacked ADP-ribosyltransferase activity in vitro, was not completely obliterated and cyclic AMP was partially induced in the target cells, showing that they still displayed enzymic activity in vivo. Moreover, although the A subunit possesses three potential sites for cleavage by furin, furin was not involved in the partial toxicity and cyclic AMP induction observed. These data suggest that target cells have a nick mechanism that operates at sites other than those around Arg192 or those recognized by furin, which generates an active fragment by processing the A subunit after toxin binding to the cell membrane.
Tsuji
Takao
T
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
Kato
Michio
M
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
Kawase
Hidetsugu
H
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
Imamura
Seiji
S
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
Kamiya
Hirofumi
H
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
Ichinose
Yoshio
Y
Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852, Japan.
Miyama
Akio
A
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity; D001665:Binding Sites; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D045683:Furin; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009152:Mutagenicity Tests; D013381:Subtilisins / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D001120:Arginine; C027538:heat-labile enterotoxin, E coli; D000242:Cyclic AMP; D036002:ADP Ribose Transferases; D003850:Deoxyribonuclease I; D013381:Subtilisins; D045683:Furin