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Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection
Published on: July 21, 2022
Intrinsic disorder in flaviviral capsid proteins and its role in pathogenesis
Anirudh Sundar1, Pavithra Umashankar, Priyanka Sankar
1Department of Biotechnology, Anna University, Guindy, Chennai 600 025, India.
Abstract:
A high level of disorder in many viral proteins is a direct consequence of their small genomes, which makes interaction with multiple binding partners a necessity for infection and pathogenicity. A segment of the flaviviral capsid protein (C), also known as the molecular recognition feature (MoRF), undergoes a disorder-toorder transition upon binding to several protein partners. To understand their role in pathogenesis, MoRFs were identified and their occurrence across different flaviviral capsids were studied. Despite lack of sequence similarities, docking studies of Cs with the host proteins indicate conserved interactions involving MoRFs across members of phylogenetic subclades. Additionally, it was observed from the protein-protein networks that some MoRFs preferentially bind proteins that are involved in specialized functions such as ribosome biogenesis. The findings point to the importance of MoRFs in the flaviviral life cycle, with important consequences for disease progression and suppression of the host immune system. Potentially, they might have impacted the way flaviviruses evolved to infect varied hosts using multiple vectors.
Insights
Flaviviral capsid proteins contain disordered regions called molecular recognition features (MoRFs) that are crucial for viral infection and pathogenicity. These MoRFs enable essential interactions, influencing viral evolution and host immune suppression.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Viral proteins often exhibit high disorder due to small genomes, necessitating interactions with multiple host partners for infection.
- Flaviviral capsid proteins (C) contain intrinsically disordered regions known as molecular recognition features (MoRFs).
- These MoRFs undergo a disorder-to-order transition upon binding to various protein partners.
Purpose of the Study:
- To identify MoRFs in flaviviral capsid proteins.
- To investigate the occurrence and role of MoRFs across different flaviviruses.
- To understand the contribution of MoRFs to viral pathogenesis and host interactions.
Main Methods:
- Identification of MoRFs within flaviviral capsid protein sequences.
- Computational docking studies to analyze interactions between capsid proteins and host proteins.
- Analysis of protein-protein interaction networks.
Main Results:
- MoRFs were identified in flaviviral capsid proteins, playing a key role in protein binding.
- Despite sequence divergence, conserved interactions involving MoRFs were observed across flaviviral subclades.
- Certain MoRFs preferentially bind host proteins involved in critical cellular functions like ribosome biogenesis.
Conclusions:
- MoRFs are vital for the flaviviral life cycle, impacting pathogenesis and immune evasion.
- These interactions highlight the evolutionary adaptability of flaviviruses in infecting diverse hosts and vectors.
- MoRFs represent significant targets for understanding and potentially controlling flaviviral diseases.
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