Toxins 2015, 7(7), 2674-2684; doi:10.3390/toxins7072674
A Conformational Shift in the Dissociated Cholera Toxin A1 Subunit Prevents Reassembly of the Cholera Holotoxin
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA
†
These authors contributed equally to the work.
‡
Current Address: Valencia College, 1800 South Kirkman Road, Orlando, FL 32811, USA;
*
Author to whom correspondence should be addressed.
Academic Editor: Emmanuel Lemichez
Received: 11 June 2015 / Revised: 9 July 2015 / Accepted: 14 July 2015 / Published: 20 July 2015
(This article belongs to the Special Issue The Cell Biology of Toxins and Effector Proteins from Vibrio cholerae)
Abstract
Cholera toxin (CT) consists of a catalytic A1 subunit, an A2 linker, and a homopentameric cell-binding B subunit. The intact holotoxin moves by vesicle carriers from the cell surface to the endoplasmic reticulum (ER) where CTA1 is released from the rest of the toxin. The dissociated CTA1 subunit then shifts to an unfolded conformation, which triggers its export to the cytosol by a process involving the quality control system of ER-associated degradation (ERAD). We hypothesized that the unfolding of dissociated CTA1 would prevent its non-productive reassociation with CTA2/CTB5. To test this prediction, we monitored the real-time reassociation of CTA1 with CTA2/CTB5 by surface plasmon resonance. Folded but not disordered CTA1 could interact with CTA2/CTB5 to form a stable, functional holotoxin. Our data, thus, identified another role for the intrinsic instability of the isolated CTA1 polypeptide in host-toxin interactions: in addition to activating the ERAD translocation mechanism, the spontaneous unfolding of free CTA1 at 37 °C prevents the non-productive reassembly of a CT holotoxin in the ER. View Full-TextKeywords:
cholera toxin; endoplasmic reticulum; protein disulfide isomerase; surface plasmon resonance; toxin assembly; toxin instability
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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MDPI and ACS Style
Taylor, M.; Curtis, D.; Teter, K. A Conformational Shift in the Dissociated Cholera Toxin A1 Subunit Prevents Reassembly of the Cholera Holotoxin. Toxins 2015, 7, 2674-2684.