'Micro' Organism, 'Macro' Problems

 

Chun-Hua Hsu (徐駿森)

Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan

 


Abstract:

Macro domains, an ancient and diverse protein family, are key players in the recognition, interpretation, and turnover of ADP-ribose signaling in the form of a derived metabolite or as a modification covalently bound to proteins. Due to macro domains sharing similar fold but regulating a wide variety of cellular processes, we attempted to extensively study this protein family and zoom in on molecular details by using structural biology, along with biochemical and biophysical approach. Intriguingly, we found several previously unperceived events, including the NAD metabolites binding of viral macro domains, the novel yeast 3”-O-Acetyl-ADP-ribose deacetylase, and the existence of a poly-ADP-ribosylation system in bacteria. The findings not only expand the structural and functional diversification of Macro domains in microorganism but support their novel biological roles and emerging potential as therapeutic targets.

  

Keywords – macro domain; ADP-ribose; coronavirus; poly-ADP-ribosylation; OAADPR

 

References:

  1. Y-C. Chiu, M.-C. Tseng, and C.-H. Hsu*, “Expanding the Substrate Specificity of Macro Domains toward 3”-isomer of O-Acetyl-ADP- ribose.” ACS Catalysis, 11(17), 11075–11090, September 2021.
  2. M-H. Lin, Y.-P. Huang, C.-F. Chang, and C.-H. Hsu*, “NMR Assignments of the Macro Domain from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).” Biomolecular NMR Assignments, 15(1):137-142, April 2021.
  3. M-H. Lin, C.-C. Cho, Y.-C. Chiu, C.-Y. Chien, Y.-P. Huang, C.-F. Chang, and C.-H. Hsu*, “Elucidating the Tunability of Binding Behavior for the MERS-CoV Macro Domain with NAD Metabolites.” Communications Biology, 4(1):123, January 2021.
  4. M-H. Lin, S.-C. Chang, Y.-C. Chiu, B.-C. Jiang, T.-H. Wu, and C.-H. Hsu*, “Structural, Biophysical and Biochemical Elucidation of the SARS-CoV-2 Nonstructural Protein 3 Macro Domain.” ACS Infectious Diseases, 6(11):2970–2978, November 2020.
  5. C-C. Cho, C.-Y. Chien, Y.-C. Chiu, M.-H. Lin, and C.-H. Hsu*, “Structural and Biochemical Evidence Supporting Poly ADP-ribosylation in the Bacterium Deinococcus radiodurans.” Nature Communications, 10:1491, April 2019.
  6. Y-P Huang, C.-C. Cho, C.-F. Chang*, and C.-H. Hsu*, “NMR Assignments of the Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV).” Biomolecular NMR Assignments, 10(2):245-248, October 2016.
  7. C-C. Cho, M.-H. Lin, C.-Y. Chuang, and C.-H. Hsu*, “Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an Efficient ADP-ribose Binding Module: Crystal Structure and Biochemical Studies.” Journal of Biological Chemistry, 291:4894- 4902, March 2016.

 


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