Year: 2013
Type: article
Abstract: Pathogenic strains of Escherichia coli produce a number of toxins that belong to the AB 5 toxin family, which comprise a catalytic A-subunit that induces cellular dysfunction and a B-pentamer that recognizes host glycans. Although the molecular actions of many of the individual subunits of AB 5 toxins are well understood, how they self-associate and the effect of this association on cytotoxicity are poorly understood. Here we have solved the structure of the holo-SubAB toxin that, in contrast to other AB 5 toxins whose molecular targets are located in the cytosol, cleaves the endoplasmic reticulum chaperone BiP. SubA interacts with SubB in a similar manner to other AB 5 toxins via the A2 helix and a conserved disulfide bond that joins the A1 domain with the A2 helix. The structure revealed that the active site of SubA is not occluded by the B-pentamer, and the B-pentamer does not enhance or inhibit the activity of SubA. Structure-based sequence comparisons with other AB 5 toxin family members, combined with extensive mutagenesis studies on SubB, show how the hydrophobic patch on top of the B-pentamer plays a dominant role in binding the A-subunit. The structure of SubAB and the accompanying functional characterization of various mutants of SubAB provide a framework for understanding the important role of the B-pentamer in the assembly and the intracellular trafficking of this AB 5 toxin. Background: AB 5 toxins consist of a pentameric B-subunit and a catalytic A-subunit. Results: Crystallographic data, dissociation, and intracellular trafficking of SubAB toxin are reported. Conclusion: SubAB architecture is similar to other AB 5 toxins, whereas the B-pentamer plays an important role in assembly and intracellular trafficking. Significance: The conserved hydrophobic ring in the B-pentamer supports the view that A- and B-subunits have evolved independently.
Source: Journal of Biological Chemistry
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1996415937