Structure and action of CARDS toxin

University Of Texas Hlth Science Center, San Antonio TX

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Abstract

Asthma is a complex disorder characterized by episodic airway obstruction and hyper-responsiveness, sometimes accompanied by airway remodeling. Although the underlying causes of asthma remain poorly understood, one contributing factor is exposure to respiratory pathogens. For example, asthmatics positive for Mycoplasma pneumoniae (M. pneumoniae) infection have demonstrated an improvement in pulmonary function after antibiotic treatment whereas patients that test negative do not, suggesting a causal relationship between M. pneumoniae infection and asthma symptom severity. Although there is a strong clinical correlation between M. pneumoniae infection and a sub-set of asthma cases, until recently, the identification of a virulence factor that might play a role in disease pathogenesis had remained elusive. This situation changed, however, when we discovered a 591 amino acid protein with ADP-ribosyltransferase (ART) activity in M. pneumoniae designated Community Acquired Respiratory Distress Syndrome ToXin (CARDS TX). The experiments outlined in this proposal are designed to uncover the structure and action of CARDS TX using a range of biophysical techniques. Using the well-established tools of single crystal X-ray diffraction, we will determine: 1) the three-dimensional structure of CARDS TX; 2) CARDS TX in complex with its NAD