Activation and mechanism of Clostridium septicum alpha toxin.
Clostridium septicum produces a single lethal factor, alpha toxin (AT), which is a cytolytic protein with a molecular mass of approximately 48 kDa. The 48 kDa toxin was found to be an inactive protoxin (ATpro) which could be activated via a carboxy-terminal cleavage with trypsin. The cleavage site was located approximately 4 kDa from the carboxy-terminus. Proteolytically activated ATpro had a specific activity of approximately 1.5 x 10(6) haemolytic units mg-1. The trypsin-activated toxin (ATact) was haemolytic, stimulated a prelytic release of potassium ions from erythrocytes which was followed by haemoglobin release, induced channel formation in planar membranes and aggregated into a complex of M(r) > 210,000 on erythrocyte membranes. ATpro did not exhibit these properties. ATact formed pores with a diameter of at least 1.3-1.6 nm. We suggest that pore formation on target cell membranes is responsible for the cytolytic activity of alpha toxin.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
J
J
Ballard
Y
Y
Sokolov
W L
WL
Yuan
B L
BL
Kagan
R K
RK
Tweten
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003013:Clostridium / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006460:Hemolysin Proteins / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C064270:hemolytic toxin, Clostridium septicum; D014357:Trypsin; D011188:Potassium