Diphtheria toxin fragment forms large pores in phospholipid bilayer membranes.
The cytotoxic effect of diphtheria toxin requires the entry of its enzymatic A fragment (Mr approximately 21,000) into the cytosol of sensitive cells. We show that the B45 fragment (Mr approximately 24,000) forms, in lipid bilayers, pores that are large enough (diameter greater than or equal to 18 A) to allow the passage of extended fragment A. Pore formation is maximal when the B45-containing side is at low pH (4.7) and the opposite side is at high pH (7.4). These conditions resemble the pH gradient existing across lysosomal membranes. We suggest that fragment A passes through these pores from acidic endocytotic vesicles (lysosomes?) to the cytosol.
D003217:Conductometry; D003429:Cross Reactions; D004167:Diphtheria Toxin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects*; D008051:Lipid Bilayers; D008081:Liposomes; D008564:Membrane Potentials; D010446:Peptide Fragments; D010743:Phospholipids; D013329:Structure-Activity Relationship
D004167:Diphtheria Toxin; D007473:Ion Channels; D008051:Lipid Bilayers; D008081:Liposomes; D010446:Peptide Fragments; D010743:Phospholipids