Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease

Autor: Matthew R. Goode, Tien L. Olson, Jun Liu, Alicia M. Saarinen, Emily K. Kaschner, Petra Fromme, Felicia M. Craciunescu, James Zook, Debra T. Hansen, Michael W. Moran, Elizabeth P. Ramirez, Vasiliki Laloudakis, Bobby Baravati
Rok vydání: 2020
Předmět:
Cirrhosis
Magnetic Resonance Spectroscopy
Light
Hydrolases
Cell Cycle Proteins
Type 2 diabetes
Chronic liver disease
Spectrum analysis techniques
Biochemistry
Small-Angle Scattering
Scattering
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Medicine and Health Sciences
Macromolecular Structure Analysis
Lipases
Materials
chemistry.chemical_classification
0303 health sciences
Multidisciplinary
Chemistry
Liver Diseases
Physics
Electromagnetic Radiation
Fatty liver
Enzymes
Physical Sciences
Medicine
medicine.symptom
Research Article
Protein Structure
Science
Materials Science
030209 endocrinology & metabolism
Inflammation
Gastroenterology and Hepatology
03 medical and health sciences
Insulin resistance
NMR spectroscopy
medicine
Animals
Humans
Molecular Biology
030304 developmental biology
Light Scattering
Biology and Life Sciences
Proteins
medicine.disease
Research and analysis methods
Fatty Liver
Enzyme
Oligomers
Adipose triglyceride lipase
Enzymology
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 7, p e0249164 (2021)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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