The arrangement of subunits in chlorea toxin

Abstract

Cholera toxin consists of five similar B subunits of apparent molecular weight about 10 600 and one A subunit (29 000) consisting of two peptides (A1 23 000-24 000 and A2 about 5500) linked by a single disulfide bond. Each B subunit also contains one internal disulfide bond which is readily reduced but is protected from carboxymethylation unless the reduced subunits are heated in urea. Tyrosine residues in A1 and in B subunits are readily iodinated, but the intact B assembly does not react with iodine. Upon reaction with the cross-linking reagent dimethyl suberimidate, B subunits may be covalently connected to each other, to A1 and to A2. A1 and A2 may also be cross-linked. The B subunits are probably arranged in a ring with A on the axis. A2 is required for the re-assembly of toxin from its subunits and may serve to hold A1 on the B ring. The maximum activity of cholera toxin in vitro is obtained only when the active peptide, A1, is separated from the rest of the molecule. Such separation, and the insertion of A1 into the cytosol, must follow the binding of the complete toxin, through component B, to the exterior of intact cells. This binding increases the effective concentration of the toxin in the vicinity of the plasma membrane. Possible ways in which A1 then crosses the membrane are considered in the Discussion.

Transport of proteins into mitochondria and chloroplasts.

“…Other examples are cholera toxin and Pseudornonas toxin, both of which traverse animal cell membranes in much the same way as diphtheria toxin. For instance, the A and B subunits of cholera toxin are not linked by disulfide bonds but, instead, are held together by noncovalent forces (46). The B subunits bind specifically to a membrane receptor which has been identified as ganglioside GM1 (120).…”

Bacillus anthracisEdema Toxin Acts as an Adjuvant for Mucosal Immune Responses to Nasally Administered Vaccine Antigens

“…Cholera toxin (CT) and the related heat labile toxin I (LT-I) of Escherichia coli are AB-type toxins made of pentameric-binding B subunits and enzymatic A subunits with ADP-ribosyl transferase activities (21)(22)(23). The B subunits of CT and LT-I bind to GM1 gangliosides on target cells (24), while the more promiscuous B subunit of LT-I also exhibits affinity for GM2 and asialo-GM1 (25)(26)(27).…”

Regulation of Toxin Biosynthesis by Plasmids in Vibrio cholerae

“…I I\i T R 0 DUCT 1 0 N Cholera toxin produced by Vibrio cholerae is a multimeric protein consisting of one A and five B subunits (Gill, 1976), and the genes encoding and regulating toxin biosynthesis appear to be located on the V. cholerae chromosome (Mekalanos et al, 1979;Sporecke et al, 1984). Sinha & Srivastava (1978a, b) observed suppression of virulence of V. cholerae after acquisition of P and/or V plasmids, which was associated with partial or complete inhibition of toxin biosynthesis.…”