3D Structure of Cholera Toxin
On this page, you can see a 3D structure of the cholera toxin protein. Cholera toxin is secreted by the bacterium
Vibrio cholerae and is responsible for the debilitating symptoms and effects of cholera infection.
It is a secreted heterohexameric AB5 enterotoxin. Throughout this tutorial, I will attempt to highlight the structural aspects
of cholera toxin that are directly related to its function and infectious nature.
Reset and spin the cholera toxin protein.
Notice that the cholera toxin is composed of three distinct subunits. The wedge-shaped A1 subunit (red) sits
above the pentameric B subunits (yellow), and is loosely held together by a connecting A2 chain (green).
Here is another view of the cholera toxin protein. Note that it is composed of both alpha helices and
beta strands. The A1 subunit (red) is composed of both types of secondary structure, the A2 subunit (green)
is one alpha helix, and the B pentamer (yellow) is composed of both types of secondary structure.
The structure of the targeting B subunits promotes detection and binding of GM1 gangliosides
which are exposed on the surface of intestinal epithelial cells. The five units of the B pentamer are highlighted
here (yellow, magenta, green, red, blue). Note that the B subunits assume a stable pentamer shape with five-fold symmetry, and each of the B
monomers surround the central pore.
Notice that each of the B monomers has has its own equivalent site for GM1 ganglioside binding (green).
The GM1 gangliosides are exposed on the luminal surface of intestinal epithelial cells and are believed to bind
to the B pentamer (magenta) with the toxin facing the membrane surface. The presence of five separate binding sites in one
molecule of toxin suggests that cholera toxin is highly efficient in recognition of target cells.
Now look at the A subunits. The entire A subunit is translated as one single protein that is nicked by a bacterial
endoprotease to form the enzymatic A1 subunit (green) and the connector A2 chain (yellow). Both subunits are loosely
folded. The two chains are held together by extensive non-covalent forces and a single intrachain disulfide bond (red).
The A1 chain is the cytotoxic part of the protein and is capable of binding NAD and catalyzing the ADP-ribosylation of G-protein.
The enzymatic A1 chain has a substructure of three units: the A1-1 (blue) subunit forms a compact globular unit of a mixture of alpha
helices and beta strands. The A1-2 (orange) subunit forms a bridge between the A1-1 and A1-3 domains. The A1-3 (green) subunit
is a globular structure that surrounds the disulfide bridge linking A1 and A2 fragments.
Notice how the A2 chain (spacefill) connects the A1 fragment (white) to the B pentamer (pink). The A2 chain is crucial for toxin assembly and successful functioning
since there are few direct stabilizing interactions between A1 and B. The A2 subunit assumes a complete alpha-helical structure except for
a 52-degree kink in the central portion of the protein. There are three discrete units of the A2 chain: an amino-terminal helix (green),
a length of chain that winds through the pore of the B pentamer (blue), and a carboxyl-terminal helix (red).
It is interesting to note that the last four residues of the A2 chain are KDEL (red), which is an endoplasmic reticulum retention signal
and integral for toxin stability.
All references and sources were obtained from this full description of the structure and function of cholera toxin protein:
Cholera Toxin Description
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