SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity
| Autor: | Chiung-Yao Chen, Yue-Li Juang, Wei-Yen Wei, Shen-Kao Lee, Hsin-Chieh Ma, Chee-Hing Yang, Chia-Wen Wang, Shih-Yen Lo, Hui-Chun Li |
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| Rok vydání: | 2011 |
| Předmět: |
Pyruvate dehydrogenase kinase
Immunoprecipitation viruses Pyruvate Kinase HuH7 Cell Plasma protein binding PKM2 Biology Severe Acute Respiratory Syndrome Cell Line Virology Two-Hybrid System Techniques Protein Interaction Mapping Animals Humans Protein Interaction Domains and Motifs skin and connective tissue diseases Microscopy Confocal fungi General Medicine Transfection Nucleocapsid Proteins Molecular biology Pyruvate Kinase Activity Yeast body regions Severe acute respiratory syndrome-related coronavirus Cell culture Murine Hepatitis Virus Type Host-Pathogen Interactions Original Article Pyruvate kinase Protein Binding |
| Zdroj: | Archives of Virology |
| ISSN: | 1432-8798 |
| Popis: | The pathogenesis of SARS-CoV remains largely unknown. To study the function of the SARS-CoV nucleocapsid protein, we have conducted a yeast two-hybrid screening experiment to identify cellular proteins that may interact with the SARS-CoV nucleocapsid protein. Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment. The binding domains of these two proteins were also determined using the yeast two-hybrid system. The physical interaction between the SARS-CoV nucleocapsid and cellular pyruvate kinase (liver) proteins was further confirmed by GST pull-down assay, co-immunoprecipitation assay and confocal microscopy. Cellular pyruvate kinase activity in hepatoma cells was repressed by SARS-CoV nucleocapsid protein in either transiently transfected or stably transfected cells. PK deficiency in red blood cells is known to result in human hereditary non-spherocytic hemolytic anemia. It is reasonable to assume that an inhibition of PKL activity due to interaction with SARS-CoV N protein is likely to cause the death of the hepatocytes, which results in the elevation of serum alanine aminotransferase and liver dysfunction noted in most SARS patients. Thus, our results suggest that SARS-CoV could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease. |
| Databáze: | OpenAIRE |
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