Chapter 3 : Shiga Toxin (Stx) Classification, Structure, and Function

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Shiga toxin (Stx) is one of the most potent biological poisons known. Stx causes fluid accumulation in rabbit ileal loops; causes renal damage in mice, rabbits, greyhounds, and baboons; and is lethal to animals upon injection. However, humans encounter Stx as a consequence of infection with type 1 or certain serogroups of such as O157:H7. There are two immunologically distinct groups of Stxs, and this review discusses toxin classification, structure, and function and the virulence associated with Stx-producing (STEC).

Citation: Melton-Celsa A. 2015. Shiga Toxin (Stx) Classification, Structure, and Function, p 37-53. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0024-2013
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Image of Figure 1
Figure 1

Cartoon representation of the Stx structure. The active-site glutamic acid is indicated as a vertical blue line, the ribosome interaction region is shown in purple, the protease (furin)- sensitive site is depicted in green, and the B pentamer as an orange block. The disulfide bridge that connects the A subunit and the A peptide is shown above the protease-sensitive site. A region important for translocation from the ER to the cytosol is indicated by a bracket. Not to scale.

Citation: Melton-Celsa A. 2015. Shiga Toxin (Stx) Classification, Structure, and Function, p 37-53. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0024-2013
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Image of Figure 2
Figure 2

Ribbon diagram of the Stx1 crystal structure. The B pentamer is shown in orange and the A in blue. The majority of the A is depicted in green except for the region that interacts with the ribosome, which is shown in purple. The active residue 167 is red, and other active-site side chains are pale blue. The A chain is medium blue, and the B subunits are orange. The structure (1R4Q) was drawn with PyMOL Molecular Graphics System, Version 1.5.0, Schrödinger, LLC. Figure kindly provided by Dr. James Vergis.

Citation: Melton-Celsa A. 2015. Shiga Toxin (Stx) Classification, Structure, and Function, p 37-53. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0024-2013
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Image of Figure 3
Figure 3

An illustration of the retrograde pathway for Stxs. The toxin binds to Gb3 within lipid rafts that contain cholesterol and that complex is internalized within an endosome. From the endosome the toxin traffics to the Golgi where it is nicked by furin if that nicking did not occur in the intestine. The nicked toxin moves to the ER where the disulfide bridge that keeps the A tethered to AB5 is reduced. The A chain then enters the cytosol and removes an adenine residue from the 28S ribosome.

Citation: Melton-Celsa A. 2015. Shiga Toxin (Stx) Classification, Structure, and Function, p 37-53. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0024-2013
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Prototype toxins and strains that produce those toxins

Citation: Melton-Celsa A. 2015. Shiga Toxin (Stx) Classification, Structure, and Function, p 37-53. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0024-2013

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