Generation of a membrane-bound, oligomerized pre-pore complex is necessary for pore formation by Clostridium septicum alpha toxin.

摘要: Department of Psychiatry, UCLA NeuropsychiatricInstitute and the West Los Angeles ofVeterans Affairs Medical Center, Angeles, California90025, USA.SummaryLow-temperature inhibition cytolytic activityof alpha toxin has facilitated identification animportant step in mechanism thistoxin. When toxin-dependent haemolysis wasmeasured on erythrocytes at various temperatures itwas clear that #158C haemolysisratewas significantly inhibited with little or no haemo-lysis occurring 48C. Alpha appeared to bindto oligomerize erythrocyte membranes withsimilar kinetics 48C 378C. The slight differ-ences these two processes 378C couldnot account for loss activity lowtemperature. At neither stimulatedpotassium release from nor formed poresin planar membranes. In contrast, temperatures$258C both proceeded rapidly. Pores thatwere opened osmotically stabilized erythrocytescould not be closed by low temperature. Therefore,low temperature prevent oligomer-ized complex forming a pore membrane.These data support hypothesis toxinoligomerizes into membrane-bound, pre-pore com-plex prior formation lipid bilayer.IntroductionAlpha is major lethal factor produced Clos-tridium septicum, cause non-traumatic gasgangrene humans (Stevens et al., 1990). We havedetermined its mechanismis based target membrane(Ballard 1993). It synthesized secreted asan inactive protoxin (AT