Toxin nicked

Sandvig, K., and Olsnes, S. (1981) Rapid entry of nicked diphtheria toxin into cells at low pH. Characterization of the entry process and effects of low pH on the toxin molecule. /. Biol. Cbem. 256, 9068. 

The BoNT/A hdotoxin is depicted as a three-dimensional ribbon structure containing the LC and HC portions. While synthesized as a single polypeptide, proteases in the gut nick the toxin and cxrnvert it to its fully activated dichain twm. 

Ohno-lwashita Y, Ywamoto M, Mitsui K et al. (1988) Protease nicked 0-toxin of Clostridium perfringens a new membrane probe with no catalytic effect reveals two classes of cholesterol as toxin-binding sites on sheep eryfhrocytes. In Eur J Biochem 176 95-101. 

Palmer M, Weller U, MeBner M et al. (1993) Altered pore-forming properties of proteolytically nicked staphylococcal a-toxin. In J Biol Chem 268 11963-11967. 

Fig. 1. Schematic structure of intact and nicked diphtheria toxin (a) and of a fusion protein where a passenger protein has been fused to the N-terminus of the A-fragment (b)...

Diphtheria toxin is produced as a single polypeptide chain (Fig. la) yyhich is easily cleaved ("nicked") by trypsin and trypsin-like proteases into two disulfide-linked fragments, A and B (Pappenheimer, 1977). The structure of the nicked toxin resembles that of the plant toxins ricin, abrin, modeccin, viscumin and others (Olsnes and Sandvig, 1985). 

Moskaug J0, Sandvig K, Olsnes S (1987) Cell-mediated reduction of the interfragment disulfide in nicked diphtheria toxin. A new system to study toxin entry at low pH. J Biol Chem 262 10339-10345. 

Fig. 2. Immunoblot analysis of crude periplasmic extracts of E. coli (pABI508) following SDS-polyacrylamide gel electrophoresis and transfer to nitrocellulose paper. Lane A, E. cc //(pABI508) extracts probed with monoclonal antibody to recombinant IL-2 Lane B, E. c<9//(pABI508) extracts probed with polyclonal anti-diphtheria toxin serum Lane C, partially "nicked" diphflieria toxin probed with anti-toxin. Apparent molecular weights x 10- are indicated.

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