Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin fromMycoplasma pneumoniae

Author:

Becker Argentina,Kannan T. R.,Taylor Alexander B.,Pakhomova Olga N.ORCID,Zhang Yanfeng,Somarajan Sudha R.,Galaleldeen Ahmad,Holloway Stephen P.,Baseman Joel B.,Hart P. John

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 β-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 β-trefoil domain. The results enhance our understanding ofMppathogenicity and suggest a novel avenue for the development of therapies to treatMp-associated asthma and other acute and chronic airway diseases.

Funder

Office of Extramural Research, National Institutes of Health

Welch Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference49 articles.

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