In the United States
non-alcoholic fatty liver disease (
NAFLD) is the most common form of chronic
liver disease, affecting an estimated 80 to 100 million people. It occurs in every age group, but predominantly in people with risk factors such as
obesity and
type 2 diabetes.
NAFLD is marked by fat accumulation in the liver leading to liver
inflammation, which may lead to
scarring and irreversible damage progressing to
cirrhosis and
liver failure. In animal models, genetic ablation of the
protein G0S2 leads to alleviation of liver damage and
insulin resistance in high fat diets. The research presented in this paper aims to aid in rational based drug design for the treatment of
NAFLD by providing a pathway for a
solution state NMR structure of G0S2. Here we describe the expression of G0S2 in an E. coli system from two different constructs, both of which are confirmed to be functionally active based on the ability to inhibit the activity of Adipose
Triglyceride Lipase. In one of the constructs, preliminary NMR spectroscopy measurements show dominant alpha-helical characteristics as well as resonance assignments on the N-terminus of G0S2, allowing for further NMR work with this
protein. Additionally, the characterization of G0S2 oligomers are outlined for both constructs, suggesting that G0S2 may defensively exist in a multimeric state to protect and potentially stabilize the small 104
amino acid protein within the cell. This information presented on the structure of G0S2 will further guide future development in the
therapy for
NAFLD.