Document Type
Article
Publication Date
4-2015
Publication Title
Proceedings of the National Academy of Sciences
Volume
112
Issue
16
Pages
5165-5170
DOI
10.1073/pnas.1420308112
Abstract
Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and "walking" pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. Here we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem beta-trefoil domains associate to form an overall architecture distinct from other well-recognized ADP-ribosylating bacterial toxins. We demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin specifically over other membrane lipids, and that cell surface binding and internalization activities are housed within the C-terminal beta-trefoil domain. The results enhance our understanding of Mp pathogenicity and suggest a novel avenue for the development of therapies to treat Mp-associated asthma and other acute and chronic airway diseases.
Original Publication Citation
Becker, A., Kannan, T.R., Taylor, A.B., Pakhomova, O.N., Zhang, Y., Somarajan, S.R., . . . Hart, P.J. (2015). Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin from Mycoplasma pneumoniae. Proceedings of the National Academy of Sciences, 112(16), 5165-5170. doi: 10.1073/pnas.1420308112
Repository Citation
Becker, Argentina; Kannan, T. R.; Taylor, Alexander B.; Pakhomova, Olga N.; Zhang, Yanfeng; Somarajan, Sudha R.; Galaleldeen, Ahmad; Holloway, Stephen P.; Baseman, Joel B.; and Hart, P. John, "Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating Cytotoxin from Mycoplasma Pneumoniae" (2015). Bioelectrics Publications. 27.
https://digitalcommons.odu.edu/bioelectrics_pubs/27