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.
Ballard
J
J
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Sokolov
Y
Y
Yuan
W L
WL
Kagan
B L
BL
Tweten
R K
RK
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