Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.9
Classification:TOXIN, TRANSFERASE
Release Date:2015-04-08
Deposition Date:2014-05-30
Revision Date:2015-04-22#2015-05-13#2017-09-27
Molecular Weight:411598.47
Macromolecule Type:Protein
Residue Count:3546
Atom Site Count:28596
DOI:10.2210/pdb4tlv/pdb
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.
Resolution:1.9
Classification:TOXIN, TRANSFERASE
Release Date:2015-04-08
Deposition Date:2014-05-30
Revision Date:2015-04-22#2015-05-13#2017-09-27
Molecular Weight:411598.47
Macromolecule Type:Protein
Residue Count:3546
Atom Site Count:28596
DOI:10.2210/pdb4tlv/pdb
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.
Date made available | 2015 |
---|---|
Publisher | RCSB-PDB |