4TLV

CARDS TOXIN, NICKED

Summary for 4TLV

• Entry DOI: 10.2210/pdb4tlv/pdb
• Related: 4TLW
• Descriptor: ADP-ribosylating toxin CARDS, SULFATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: mycoplasma pneumoniae, virulence, atypical pneumonia, community acquired respiratory distress syndrome, adp-ribosyl transferase, toxin, transferase
• Biological source: Mycoplasma pneumoniae
• Cellular location: Cell membrane ; Peripheral membrane protein ; Extracellular side : P75409
• Total number of polymer chains: 6
• Total formula weight: 411598.46

Authors

Taylor, A.B.,Pakhomova, O.N.,Hart, P.J. (deposition date: 2014-05-30, release date: 2015-04-08, Last modification date: 2024-10-30)

Primary citation

Becker, A.,Kannan, T.R.,Taylor, A.B.,Pakhomova, O.N.,Zhang, Y.,Somarajan, S.R.,Galaleldeen, A.,Holloway, S.P.,Baseman, J.B.,Hart, P.J.
Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin from Mycoplasma pneumoniae.
Proc.Natl.Acad.Sci.USA, 112:5165-5170, 2015

PubMed 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.

PubMed: 25848012
DOI: 10.1073/pnas.1420308112

Experimental method

X-RAY DIFFRACTION (1.9 Å)