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• W4210997355 endingPage "549" @default.
• W4210997355 startingPage "509" @default.
• W4210997355 abstract "1. Death in several infectious diseases is caused by protein toxins secreted by invading bacteria. Cholera toxin is a simple protein secreted by Vibrio cholerae colonizing the gut; it is responsible for the massive diarrhoea that is cholera. 2. The primary action of cholera toxin is an activation of adenylate cyclase, an enzyme found on the inner membrane of eukaryotic cells that catalyses the conversion of ATP to cyclic AMP. Consequent increases in the intracellular concentration of cyclic AMP are responsible for other manifestations of cholera toxin including the diarrhoea. The toxin is active on almost all eukaryotic cells. 3. The toxin can be purified from culture filtrates of V. cholera. It has a molecular weight of 82000; and is composed of one subunit A (itself two polypeptide chains joined by a disulphide bond: AI (22000) and A2 (5000)) and five subunits B (11500). These can be separated in dissociating solvents such as detergents or 6 M guanidine hydrochloride. An amino-acid sequence of subunit B has been published. The five B subunits (sometimes found by themselves in the filtrate and known as ‘choleragenoid’) are probably arranged in a ring with the subunit A in the middle joined to them non-covalently by peptide A2. 4. The first action of cholera toxin on a cell is to bind to the membrane strongly and irreversibly. Several thousand molecules of toxin bind to each cell and the binding constants are of the order of 10-10 M. The binding is rapid, but is followed by a lag phase of about an hour before the intracellular cyclic AMP concentration begins to increase. 5. Ganglioside GM1, a complex amphiphilic lipid found in cell membranes, binds tightly to the toxin which shows an enzyme-like specificity for this particular ganglioside. Toxin that has already bound ganglioside can no longer bind to cells and is therefore inactive. This and other experiments using cells depleted of endogenous ganglioside suggest that ganglioside GM1 is the natural receptor of the toxin on the cell surface. The binding is followed by a lateral movement of the toxin-ganglioside complex in the cell surface forming a ‘cap’ at one pole of the cell. 6. The binding of ganglioside by toxin is a function exclusively of subunit B; Subunit A does not bind and can be eluted with 8 M urea from an insolubilized toxin-ganglioside complex. Subunit B is not by itself active, and so preincubation with B can protect cells or even whole gut from the action of toxin by occupying all the ganglioside binding sites. 7. Subunit A is responsible for activation of adenylate cyclase. Purified subunit A or just peptide AI is active by itself and this activity is not inhibited by ganglioside or by antisera to subunit B. In intact cells the activity is low and shows the characteristic lag phase but in lysed cells the subunit (or the whole toxin) is much more active and there is no lag phase. This suggests that the lag phase represents the time that subunit A takes to cross the cell membrane and get to its target. 8. Several cofactors are needed for toxin activity in lysed cells: NAD+, ATP, sulphydryl compounds and another unidentified cytoplasmic component. The activity of the cyclase is altered in a complex way generally rather similarly to the action of hormones such as adrenalin, but it is difficult to draw any general conclusions. 9. There are two chief theories of how cholera toxin acts. The first is that subunit A (or just peptide AI) enters the cell and there catalyses some reaction leading to activation of the cyclase. The cleavage of NAD+ into nicotinamide and adenosine diphosphoribose could be such a reaction; it is catalysed by high concentrations of cholera toxin. 10. The other theory is that part of the toxin binds directly to the adenylate cyclase or to some other molecule that can then interact with the cyclase, perhaps after the lateral movement of the toxin-ganglioside complex in the cell surface. This binding may be related to the known action of guanyl nucleotides on the cell surface. 11. The entry of peptide AI into the cell and its transport through the membrane is mediated by the binding of subunits B to the cell surface, perhaps just because the binding increases the local concentration of subunit A, or perhaps following specific conformational changes in the subunits and the formation of a tunnel of B subunits through the membrane. An experiment showing that the toxin remains active when the subunits are covalently bonded together suggests that peptide AI does not separate completely from the rest of the molecule. 12. There are several other proteins that resemble cholera toxin in structure and function. For example, glycoprotein hormones such as thyrotrophin also activate adenylate cyclase and have an apparently similar subunit structure with one type of subunit that binds to a ganglioside. There may also be analogies between the amino-acid sequences of toxin and hormones. 13. The enterotoxin made by some strains of Escherichia coli produces a similar diarrhoea to that of cholera. Several different toxic proteins have been prepared but they all seem to activate adenylate cyclase in the same sort of way as cholera toxin does and also to cross-react immunologically with it. The E. coli toxin also reacts with ganglioside G, but the reaction is weak and probably physiologically insignificant. Salmonella typhimurium secretes a similar toxin. 14. Tetanus toxin also reacts with a ganglioside receptor. This protein has two polypeptide chains of which only one reacts with the ganglioside; but the molecular activity is not yet known. 15. Diphtheria toxin has an A fragment that is directly responsible for the toxicity (by catalysing an NAD+ cleavage reaction leading to the total inhibition of protein synthesis) and a B fragment that gets the A fragment into the cells. This structure of active and binding components therefore seems to be common to many toxins. 16. The ability to produce toxin may confer some selective advantage on V. cholerae. The toxin may originate from accidental incorporation of DNA from an eukaryotic host, or alternatively from some material involved with the cyclic AMP metabolism of the bacterium." @default.
• W4210997355 created "2022-02-13" @default.
• W4210997355 creator A5018908340 @default.
• W4210997355 date "1977-11-01" @default.
• W4210997355 modified "2023-09-25" @default.
• W4210997355 title "CHOLERA TOXIN" @default.
• W4210997355 cites W145024411 @default.
• W4210997355 cites W1500910904 @default.
• W4210997355 cites W1505751930 @default.
• W4210997355 cites W1511737325 @default.
• W4210997355 cites W1513638021 @default.
• W4210997355 cites W1518896112 @default.
• W4210997355 cites W1532520741 @default.
• W4210997355 cites W1538671656 @default.
• W4210997355 cites W1577643002 @default.
• W4210997355 cites W1602567079 @default.
• W4210997355 cites W1789551787 @default.
• W4210997355 cites W180791406 @default.
• W4210997355 cites W1839911791 @default.
• W4210997355 cites W1906029816 @default.
• W4210997355 cites W1919079566 @default.
• W4210997355 cites W1924418294 @default.
• W4210997355 cites W1960281573 @default.
• W4210997355 cites W1964060460 @default.
• W4210997355 cites W1966720341 @default.
• W4210997355 cites W1967529159 @default.
• W4210997355 cites W1969258330 @default.
• W4210997355 cites W1970177000 @default.
• W4210997355 cites W1970271391 @default.
• W4210997355 cites W1970729813 @default.
• W4210997355 cites W1970841868 @default.
• W4210997355 cites W1971160639 @default.
• W4210997355 cites W1971788010 @default.
• W4210997355 cites W1973258418 @default.
• W4210997355 cites W1975514600 @default.
• W4210997355 cites W1976314113 @default.
• W4210997355 cites W1977539490 @default.
• W4210997355 cites W1978064025 @default.
• W4210997355 cites W1979700521 @default.
• W4210997355 cites W1981089905 @default.
• W4210997355 cites W1981805788 @default.
• W4210997355 cites W1987704208 @default.
• W4210997355 cites W1988334785 @default.
• W4210997355 cites W1989980897 @default.
• W4210997355 cites W1991204762 @default.
• W4210997355 cites W1993977160 @default.
• W4210997355 cites W1996497544 @default.
• W4210997355 cites W1998152163 @default.
• W4210997355 cites W2000080153 @default.
• W4210997355 cites W2001212418 @default.
• W4210997355 cites W2002813546 @default.
• W4210997355 cites W2005362253 @default.
• W4210997355 cites W2008027297 @default.
• W4210997355 cites W2012585120 @default.
• W4210997355 cites W2013811589 @default.
• W4210997355 cites W2014083277 @default.
• W4210997355 cites W2017058877 @default.
• W4210997355 cites W2023658537 @default.
• W4210997355 cites W2026237325 @default.
• W4210997355 cites W2026264692 @default.
• W4210997355 cites W2027038119 @default.
• W4210997355 cites W2027736130 @default.
• W4210997355 cites W2029001394 @default.
• W4210997355 cites W2030961350 @default.
• W4210997355 cites W2031987538 @default.
• W4210997355 cites W2034103009 @default.
• W4210997355 cites W2035323896 @default.
• W4210997355 cites W2035358096 @default.
• W4210997355 cites W2041193908 @default.
• W4210997355 cites W2041442975 @default.
• W4210997355 cites W2042977621 @default.
• W4210997355 cites W2043434918 @default.
• W4210997355 cites W2044880978 @default.
• W4210997355 cites W2047782050 @default.
• W4210997355 cites W2048048582 @default.
• W4210997355 cites W2049428504 @default.
• W4210997355 cites W2050999959 @default.
• W4210997355 cites W2053500295 @default.
• W4210997355 cites W2053809118 @default.
• W4210997355 cites W2054576990 @default.
• W4210997355 cites W2060342012 @default.
• W4210997355 cites W2061878359 @default.
• W4210997355 cites W2064027278 @default.
• W4210997355 cites W2064545893 @default.
• W4210997355 cites W2064805703 @default.
• W4210997355 cites W2067109129 @default.
• W4210997355 cites W2068938933 @default.
• W4210997355 cites W2069260686 @default.
• W4210997355 cites W2072791150 @default.
• W4210997355 cites W2072893688 @default.
• W4210997355 cites W2073249636 @default.
• W4210997355 cites W2075421874 @default.
• W4210997355 cites W2077258964 @default.
• W4210997355 cites W2078980043 @default.
• W4210997355 cites W2079260303 @default.
• W4210997355 cites W2079491912 @default.
• W4210997355 cites W208071623 @default.
• W4210997355 cites W2083976364 @default.

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