Diphtheria toxin fragment forms large pores in phospholipid bilayer membranes.

Abstract

The cytotoxic effect of diphtheria toxin (Corynebacterium diphtheriae) requires the entry of its enzymatic A fragment (MW .apprxeq. 21,000) in to the cytosol of sensitive cells. The B45 fragment (MW .apprxeq. 24,000) seemingly forms, in lipid bilayers, pores that are large enough (diameter .gtoreq. 18 .ANG.) 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. Fragment A may pass through these pores from acidic endocytotic vesicles (lysosome?) to the cytosol.