Open AccessDiphtheria toxin fragment forms large pores in phospholipid bilayer membranes.
Author(s) -
Bruce L. Kagan,
Alan Finkelstein,
Marco Colombini
Publication year - 1981
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.78.8.4950
Subject(s) - cytosol , diphtheria toxin , membrane , toxin , phospholipid , chemistry , vesicle , bilayer , corynebacterium diphtheriae , biophysics , lipid bilayer , biochemistry , diphtheria , enzyme , biology , virology , vaccination
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.