Structural Characterization of CwsA in a Lipid Bilayer with ssNMR

Abstract

Tuberculosis (TB) is a leading infectious disease killer worldwide caused by Mycobacterium tuberculosis (Mtb). According to World Health Organization (WHO), 9.6 million people became ill with TB and 1.5 million died from the disease in the year of 2014. The standard drugs currently used for the treatment of TB can be dated back to more than three decades ago, and the widespread of drug-resistance has been a major concern. In 2014, an estimated 480,000 people developed multidrug-resistant TB (MDR-TB), and among which 9.7% had extensively drug-resistant TB (XDR-TB). New anti-TB drugs are thus desperately needed. CwsA is a small integral membrane protein that belongs to Mtb cell divisome. The depletion or overproduction of CwsA has been shown to affect cell wall synthesis. The structural study of CwsA in a lipid bilayer environment is crucial to the understanding of its function. Recently, Nabanita Das obtained some preliminary PISEMA ssNMR data on oriented CwsA samples which showed the approximate TM helix core region range as well as a tilt angle of 10° with respect to the lipid normal. More detailed topological information of CwsA in a lipid bilayer environment requires the generation of better aligned OS samples. The structural characterization of CwsA will help to unravel the mechanism of Mtb cell division machinery as well as the discovery of new drug targets.