Cholera toxin

Introduction

Cholera Toxin (CT) is an enzyme secreted by the cholera causing bacterium Vibrio cholerae. It ribosylates the alpha subunit of a G-protein associated with an intestinal epithelial cell, preventing the hydrolysis of GTP bound to the same G-protein. This locks the G-protein in an active state, leading to the indefinite stimulation of adenylyl cyclase, causing a rise in cAMP concentration. This then causes water and Cl^- to leave the cell and enter the intestinal lumen, leading to the severe diarrhoea and dehydration associated with cholera^[1]. 

Structure of the Toxin 

CT is a member of the AB5 family of toxins and consists of two subunits, Alpha and Beta. The Beta subunit binds to five ganglioslide GM1 receptors on the plasma membrane and trigers endocytosis of the toxin, whilst the alpha subunit is made up of an A1 and A2 chain. These are cleaved apart once inside the cell, allowing the A1 chain to dissociate and begin its catalytic activity, leaving the A2 domain which had been anchoring the A1 chain to the Beta subunit^[2].  

References

 

1. ↑ Molecular Biology of the Cell (5th edition), Alberts et al., pg 906.
2. ↑ Daniel J.-F. Chinnapen, H. C. D. S. W. I. L., 2006. Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiology Letters, 266(2), pp. 129-137.