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.

PubMed

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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