Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 06, 2024 4 months, 2 weeks, 2 days, 19 hours, 2 minutes ago
COVID-19 News: The SARS-CoV-2 virus, which causes COVID-19, has many proteins that interact with human cells. One of these proteins, called Orf9b, has been found to activate an important enzyme known as MARK2. This enzyme plays a significant role in cell functions, including maintaining cell structure and regulating immune responses. Recent research by scientists from Tokyo Metropolitan University-Japan that is covered in this
COVID-19 News report has discovered how Orf9b interacts with MARK2 to enhance its activity.
A model of Orf9b-mediated enhancement of MARK2 activity. (A) The binding of Orf9b to the KA1 domain alters the structure of MARK2, in which the kinase domain is more active. (B) MARK2 T208A has a structure in which the binding of Orf9b does not affect its activity.
What is MARK2?
MARK2 (Microtubule Affinity-Regulating Kinase 2) is an enzyme that helps regulate cell polarity and immune responses. It's crucial for various cellular processes, including cell division and movement. MARK2 is also involved in the phosphorylation of tau, a protein associated with neurodegenerative diseases such as Alzheimer's. This enzyme's activity is carefully regulated by phosphorylation, a process that adds a phosphate group to the protein, altering its function.
The Role of Orf9b
Orf9b is a small protein encoded by the SARS-CoV-2 virus. Researchers have found that this protein can enhance the activity of MARK2. However, this enhancement is indirect. Orf9b does not directly bind to MARK2 but instead interacts with a specific region of the enzyme known as the KA1 domain. This interaction alters the enzyme's structure and increases its activity.
Understanding the Interaction
To understand how Orf9b affects MARK2, scientists conducted several experiments. They expressed MARK2 alone and in combination with Orf9b in human cells (HEK293 cells). They found that when Orf9b was present, MARK2's activity increased. However, this increase did not occur when a mutated form of MARK2, lacking the KA1 domain, was used. This suggests that the KA1 domain is essential for the interaction between Orf9b and MARK2.
Phosphorylation and MARK2 Activity
Phosphorylation at specific sites on MARK2 can either activate or inhibit its activity. The enzyme is activated by phosphorylation at the T208 site and inhibited by phosphorylation at the T595 site. Researchers discovered that Orf9b reduces phosphorylation at both these sites, thereby increasing MARK2 activity. However, this reduction alone does not fully explain the increase in activity, indicating that Orf9b's binding to the KA1 domain plays a crucial role.
Broader Implications
The findings about Orf9b and MARK2 are significant because they help us understand how SARS-CoV-2 manipulates host cell functions. By enhancing MARK2 activity, Orf9b may contribute to the virus's ability to evade the immune system and promote inflammation. MARK2 is invo
lved in the production of inflammatory cytokines, which are proteins that signal the immune system to respond to infection. Increased MARK2 activity could lead to higher levels of these cytokines, contributing to the severe inflammatory responses seen in COVID-19 patients.
Future Directions
This research opens up new avenues for understanding and potentially targeting the interactions between viral proteins and host enzymes. By exploring how Orf9b and other viral proteins interact with human enzymes, scientists can develop new strategies to combat viral infections. For instance, drugs that block Orf9b's interaction with MARK2 could potentially reduce the virus's ability to manipulate host cell functions and mitigate severe inflammatory responses.
Conclusion
The discovery of how SARS-CoV-2's Orf9b protein enhances MARK2 activity adds an important piece to the puzzle of understanding COVID-19's impact on the body. This interaction highlights the complex ways in which viruses can hijack host cell machinery to promote their survival and spread. As research continues, these insights will be crucial for developing new treatments and strategies to combat COVID-19 and other viral diseases.
The study findings were published as a research letter in the peer reviewed journal: FEBS Letters.
https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14975
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