期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 16, 页码 5165-5170出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1420308112
关键词
mycoplasma cytotoxin; single-crystal X-ray diffraction; ADP-ribosyltransferase; vacuolation; reactive airway disease
资金
- National Institutes of Health [U19 AI070412, P41 GM103403]
- Kleberg Foundation
- R.A. Welch Foundation [AQ-1399]
- US Department of Energy [DE-AC02-06CH11357]
- Office of the Vice President for Research
- San Antonio Cancer Institute Grant [P30 CA054174]
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.
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