Date of this Version
Molecular Oral Microbiology
Aggregatibacter actinomycetemcomitans is a common inhabitant of the upper aerodigestive tract of humans and non-human primates and is associated with disseminated infections, including lung and brain abscesses, pediatric infective endocarditis in children, and localized aggressive periodontitis. A. actinomycetemcomitans secretes a repeats-in-toxin protein, leukotoxin, which exclusively kills lymphocyte function-associated antigen-1-bearing cells. The toxin's pathological mechanism is not fully understood; however, experimental evidence indicates that it involves the association with and subsequent destabilization of the target cell's plasma membrane. We have long hypothesized that leukotoxin secondary structure is strongly correlated with membrane association and/or destabilization. In this study, we tested this hypothesis by analyzing lipid-induced changes in leukotoxin conformation. Upon incubation of leukotoxin with lipids that favor leukotoxin-membrane association, we observed an increase in leukotoxin α-helical content that was not observed with lipids that favor membrane destabilization. The change in leukotoxin conformation after incubation with these lipids suggests that membrane binding and membrane destabilization have distinct secondary structural requirements, suggesting that they are independent events. These studies thus provide insight into the mechanism of cell damage that leads to disease progression by A. actinomycetemcomitans.
This is the pre-peer reviewed version of the following article: Walters, M. J., Brown, A. C., Edrington, T. C., Baranwal, S., Du, Y., Lally, E. T., & Boesze-Battaglia, K. (2013). Membrane Association and Destabilization by Aggregatibacter actinomycetemcomitans Leukotoxin Requires Changes in Secondary Structures. Molecular Oral Microbiology, 28(5), 342–353. http://doi.org/10.1111/omi.12028, which has been published in final form at http://doi.org/10.1111/omi.12028. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions
Conformation, intrinsic disorder, alpha helix, unordered, lipid membrane
Walters, M. J., Brown, A. C., Edrington, T. C., Baranwal, S., Du, Y., Lally, J. T., & Boesze-Battaglia, K. (2014). Membrane Association and Destabilization by Aggregatibacter Actinomycetemcomitans Leukotoxin Requires Changes in Secondary Structures. Molecular Oral Microbiology, 28 (5), 342-353. http://dx.doi.org/10.1111/omi.12028
Date Posted: 01 March 2022
This document has been peer reviewed.