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Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5165-70. doi: 10.1073/pnas.1420308112. Epub 2015 Apr 6.

Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin from Mycoplasma pneumoniae.

Author information

1
Department of Biochemistry.
2
Department of Microbiology and Immunology/Center for Airway Inflammation Research, and.
3
Department of Biochemistry, X-Ray Crystallography Core Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229;
4
Department of Biochemistry, Frank Reidy Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508;
5
Department of Biochemistry, Department of Biological Sciences, St. Mary's University, San Antonio, TX 78228; and.
6
Department of Microbiology and Immunology/Center for Airway Inflammation Research, and baseman@uthscsa.edu pjh@biochem.uthscsa.edu.
7
Department of Biochemistry, X-Ray Crystallography Core Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229; South Texas Veterans Health Care System, US Department of Veterans Affairs, San Antonio, TX 78229 baseman@uthscsa.edu pjh@biochem.uthscsa.edu.

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 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.

KEYWORDS:

ADP-ribosyltransferase; mycoplasma cytotoxin; reactive airway disease; single-crystal X-ray diffraction; vacuolation

PMID:
25848012
PMCID:
PMC4413325
DOI:
10.1073/pnas.1420308112
[Indexed for MEDLINE]
Free PMC Article

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