Date of this Version
Molecular Oral Microbiology
Summary: 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, and localized aggressive periodontitis. Aggregatibacter 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 destabilization. In this study, we tested this hypothesis by analysing 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 provide insight into the mechanism of cell damage that leads to disease progression by A. actinomycetemcomitans. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
α-helix; Conformation; Intrinsic disorder; Lipid membrane; Unordered
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://dx.doi.org/10.1111/omi.12028
Date Posted: 08 December 2022
This document has been peer reviewed.